Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
| Profile Name | KIT T632I |
| Gene Variant Detail | |
| Relevant Treatment Approaches |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| KIT T670I | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT T670I in culture, however, with decreased potency compared to its potency against other KIT variants (PMID: 31205508). | 31205508 | |
| KIT T670I | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT T670I demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT T670I | Advanced Solid Tumor | sensitive | Cabozantinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Cometriq (Cabometyx, cabozantinib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). | 33212994 | |
| KIT T670I | gastrointestinal stromal tumor | predicted - resistant | Avapritinib | Phase I | Actionable | In a Phase I trial, patients with gastrointestinal stromal tumors harboring either KIT V654A or KIT T670I demonstrated decreased overall response rate (0%, 0/25 vs. 26%, 22/84) and increased progressive disease rate (72% vs 23%) compared to those without either KIT mutation when treated with Ayvakit (avapritinib) (PMID: 31270078; NCT02508532). | 31270078 | |
| KIT T670I | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT T670I in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). | 35194937 | |
| KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Sutent (sunitinib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). | 33212994 | |
| KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT T670I in culture (PMID: 31205508). | 31205508 | |
| KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT T670I in culture (PMID: 35194937). | 35194937 | |
| KIT T670I | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I demonstrated resistance to Gleevec (imatinib) in culture (PMID: 35194937). | 35194937 | |
| KIT T670I | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I were resistant to treatment with Gleevec (imatinib) in culture (PMID: 33212994). | 33212994 | |
| KIT T670I | melanoma | resistant | Nilotinib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Tasigna (nilotinib) (PMID: 23582185, PMID: 25594040). | 23582185 25594040 | |
| KIT T670I | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Stivarga (regorafenib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). | 33212994 | |
| KIT T670I | melanoma | resistant | Dasatinib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Sprycel (dasatinib) (PMID: 23582185, PMID: 25594040). | 23582185 25594040 | |
| KIT T670I | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case report, a patient with a gastrointestinal stromal tumor developed disease progression while being treated with Gleevec (imatinib), demonstrating a KIT T670I mutation in the progressive lesion (PMID: 15236194). | 15236194 | |
| KIT T670I | melanoma | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, Sutent (sunitinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT T670I (PMID: 23582185, PMID: 25594040). | 23582185 25594040 | |
| KIT T670I | melanoma | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Gleevec (imatinib mesylate) (PMID: 23582185, PMID: 25594040). | 23582185 25594040 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | decreased response | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated a decreased response to treatment with Stivarga (regorafenib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | decreased response | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated a decreased response to treatment with Stivarga (regorafenib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | no benefit | Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | resistant | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing a KIT W557_K558del/T670I double mutation demonstrated resistance to Sprycel (dasatinib) in culture (PMID: 17699867). | 17699867 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated resistance to Ayvakit (avapritinib) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | resistant | Nilotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing a KIT W557_K558del/T670I double mutation demonstrated resistance to Tasigna (nilotinib) in culture (PMID: 17699867). | 17699867 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited proliferation and induced apoptosis of transformed cells expressing a KIT W557_K558del/T670I double mutation in culture (PMID: 17699867). | 17699867 | |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del KIT T670I | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT T670I in culture (PMID: 31205508). | 31205508 | |
| KIT V560_Y578del KIT T670I | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, a patient-derived gastrointestinal stromal tumor (GIST) cell line co-harboring KIT V560_Y578del and KIT T670I demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). | 25239608 | |
| KIT V560_Y578del KIT T670I | gastrointestinal stromal tumor | predicted - sensitive | Copanlisib + Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Aliqopa (copanlisib) and Gleevec (imatinib) demonstrated enhanced cell growth inhibition but did not result in increased apoptosis of gastrointestinal stromal tumor cells harboring KIT V560_Y578del and KIT T670I in culture, and did not result in increased tumor growth inhibition compared to Aliqopa (copanlisib) alone in cell line xenograft models (PMID: 32371592). | 32371592 | |
| KIT V560_Y578del KIT T670I | gastrointestinal stromal tumor | sensitive | Axitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and downstream signaling, reduced proliferation, and induced cell-cycle arrest in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT T670I in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). | 31205508 | |
| KIT V560_Y578del KIT T670I | gastrointestinal stromal tumor | sensitive | Copanlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Aliqopa (copanlisib) inhibited cell growth and PI3K signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT T670I in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32371592). | 32371592 | |
| KIT V560_Y578del KIT T670I | gastrointestinal stromal tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT T670I demonstrated sensitivity to treatment with Iclusig (ponatinib) (PMID: 25239608). | 25239608 | |
| KIT V560_Y578del KIT T670I | gastrointestinal stromal tumor | sensitive | Nintedanib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ofev (nintedanib) decreased Kit phosphorylation and downstream signaling, induced cell-cycle arrest and apoptosis, and inhibited proliferation of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and T670I in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). | 35194937 | |
| KIT V560D KIT T670I | Advanced Solid Tumor | sensitive | Motesanib Diphosphate | Preclinical - Cell culture | Actionable | In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/T670I double mutation in culture (PMID: 20633291). | 20633291 | |
| KIT V560D KIT T670I | Advanced Solid Tumor | resistant | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT V560D and KIT T670I were resistant to Flumatinib in culture (PMID: 24205792). | 24205792 | |
| KIT V559D KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT T670I and KIT V559D in culture (PMID: 31205508). | 31205508 | |
| KIT V559D KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V559D and T670I in culture (PMID: 35194937). | 35194937 | |
| KIT V559D KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT V559D and KIT T670I were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT V559D KIT T670I | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and T670I were resistant to Ayvakit (avapritinib) treatment in culture (PMID: 35194937). | 35194937 | |
| KIT V559D KIT T670I | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and T670I were resistant to Gleevec (imatinib) treatment in culture (PMID: 35194937). | 35194937 | |
| KIT V559D KIT T670I | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT V559D and T670I in culture (PMID: 35194937). | 35194937 | |
| KIT V559D KIT T670I | Advanced Solid Tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and T670I were resistant to Qinlock (ripretinib) treatment in culture (PMID: 35194937). | 35194937 | |
| KIT exon11 KIT T670I | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk signaling and resulted in limited (53.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). | 29100343 | |
| KIT exon11 KIT T670I | gastrointestinal stromal tumor | predicted - sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited Kit signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). | 29100343 | |
| KIT exon11 KIT T670I | gastrointestinal stromal tumor | predicted - sensitive | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) inhibited Kit signaling, resulted in 86.7% tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). | 29100343 | |
| KIT T670I KIT D816V | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670I demonstrated resistance to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). | 31270078 | |
| KIT T670I KIT D816V | Advanced Solid Tumor | decreased response | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670I demonstrated a decreased response compared to cells expressing KIT D816V alone when treated with Rydapt (midostaurin) in culture (PMID: 31270078). | 31270078 | |
| KIT exon 11 del KIT T670I | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT T670I | gastrointestinal stromal tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I demonstrated reduced response to growth inhibition by Qinlock (ripretinib) compared to cells harboring KIT exon 11 deletion alone in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT T670I | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT T670I | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT T670I in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT exon 11 del KIT T670I | gastrointestinal stromal tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT T670I | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT T670I | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I were resistant to Gleevec (imatinib) in culture (PMID: 31085175). | 31085175 | |
| KIT Y578C | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing KIT Y578C in culture (PMID: 23567324). | 23567324 | |
| KIT W557C KIT Y578C | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing both KIT W557C and KIT Y578C in culture (PMID: 23567324). | 23567324 | |
| KIT E554_K558del | gastrointestinal stromal tumor | predicted - sensitive | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, Gleevec (imatinib) and Mektovi (binimetinib) combination treatment had manageable toxicity and resulted in a 99% pathological response and 29% RECIST response in a patient with a rectal gastrointestinal stromal tumor harboring KIT E554_K558del (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT E554_K558del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT V654A was identified as a secondary resistance mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT E562_L576del mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) treatment (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT V555_L576del KIT D820G KIT D820Y | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT D820G and KIT D820Y were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V555_L576del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 | |
| KIT Y568_L576delinsCV KIT D816E KIT D820Y | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with Qinlock (ripretinib) decreased circulating tumor DNA, resulted in stable disease lasting over 21 months in a patient with gastrointestinal stromal tumor harboring a primary KIT Y568_L576delinsCV mutation and two acquired resistance mutations, KIT D816E and KIT D820Y (PMID: 31085175; NCT02571036). | 31085175 | |
| KIT D816E | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT D816E in culture (PMID: 35194937). | 35194937 | |
| KIT D816E | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited proliferation of transformed cells expressing KIT D816E in culture (PMID: 35194937). | 35194937 | |
| KIT D816E | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT D816E in culture (PMID: 35194937). | 35194937 | |
| KIT V560_Y578del KIT D816E | gastrointestinal stromal tumor | decreased response | Sunitinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT D816E demonstrated a decreased response to treatment with Sutent (sunitinib) (PMID: 25239608). | 25239608 | |
| KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | resistant | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) demonstrated limited inhibition of Kit, Erk, and Mtor signaling and resulted in minimal (22.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 | |
| KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 | |
| KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | sensitive | Imatinib + LY294002 | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib mesylate) in combination with LY394002 resulted in enhanced tumor growth inhibition compared to monotherapy in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 | |
| KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited Kit, Erk, and Mtor signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 | |
| KIT W557_K558del KIT D816E KIT D820V | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT D816E and D820V were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring KIT W557_K558del who developed resistance to Gleevec (imatinib) (PMID: 18294292). | 18294292 | |
| KIT exon 11 del KIT D816E | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT D816E in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT D816E | gastrointestinal stromal tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT D816E in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT D816E | gastrointestinal stromal tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT D816E in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT D816E | gastrointestinal stromal tumor | decreased response | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT D816E demonstrated reduced response to growth inhibition by Sutent (sunitinib) compared to cells harboring KIT exon 11 deletion alone in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT D816E | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT D816E in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT D816E | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT D816E in culture (PMID: 31085175). | 31085175 | |
| KIT D816Y | mast cell neoplasm | predicted - resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, mouse mastocytoma cells harboring KIT D814Y (corresponds to D816Y in human) were resistant to Gleevec (imatinib) in culture (PMID: 31085175). | 31085175 | |
| KIT D816Y | Advanced Solid Tumor | resistant | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Flumatinib in culture (PMID: 24205792). | 24205792 | |
| KIT D816Y | mast cell neoplasm | predicted - sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of mouse mastocytoma cells harboring KIT D814Y (corresponds to D816Y in human) in culture (PMID: 31085175). | 31085175 | |
| KIT D816Y | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Sutent (sunitinib) in culture (PMID: 24205792). | 24205792 | |
| KIT D816Y | mast cell neoplasm | decreased response | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, mouse mastocytoma cells harboring KIT D814Y (corresponds to D816Y in human) demonstrated reduced response to growth inhibition by Sutent (sunitinib) compared to GIST cells harboring KIT exon 11 deletion in culture (PMID: 31085175). | 31085175 | |
| KIT D816Y | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816Y were resistant to Gleevec (imatinib mesylate) in culture (PMID: 16397263). | 16397263 | |
| KIT D816Y | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816Y were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). | 24205792 | |
| KIT D816Y | mast cell neoplasm | predicted - sensitive | Avapritinib | Preclinical | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and proliferation of murine mastocytoma cells harboring KIT D814Y (corresponding to human D816Y) in culture, and resulted in tumor regression in allograft animal models (PMID: 29093181). | 29093181 | |
| KIT D816Y | mast cell neoplasm | predicted - resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, mouse mastocytoma cells harboring KIT D814Y (corresponds to D816Y in human) were resistant to Stivarga (regorafenib) in culture (PMID: 31085175). | 31085175 | |
| KIT D816Y | mast cell neoplasm | predicted - sensitive | Ripretinib | Preclinical | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited proliferation of mouse mastocytoma cells harboring KIT D814Y (corresponds to D816Y in human) in culture, and resulted in tumor growth inhibition in allograft models (PMID: 31085175). | 31085175 | |
| KIT D816Y | mast cell neoplasm | predicted - sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited proliferation of a mouse mastocytosis cell line expressing KIT K816Y in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). | detail... | |
| KIT K558_G565delinsR | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib) treatment resulted in tumor regression and decreased mitotic activity in gastrointestinal stromal tumor patient derived xenograft (PDX) models harboring KIT K558_G565delinsR (PMID: 27777285). | 27777285 | |
| KIT K558_G565delinsR | gastrointestinal stromal tumor | sensitive | Cabozantinib | Preclinical - Pdx | Actionable | In a preclinical study, Cometriq (Cabometyx, cabozantinib) resulted in tumor regression, decreased mitotic activity, and increased apoptotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT K558_G565delins (PMID: 27777285). | 27777285 | |
| KIT N822I | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N822I demonstrated resistance to Gleevec (imatinib) in culture (PMID: 21689725). | 21689725 | |
| KIT N822I | Advanced Solid Tumor | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis of transformed cells expressing KIT N822I in culture (PMID: 21689725). | 21689725 | |
| KIT V559X KIT N822I | melanoma | predicted - sensitive | Imatinib + Pembrolizumab | Case Reports/Case Series | Actionable | In a clinical case study, addition of Gleevec (imatinib) to Keytruda (pembrolizumab) in a patient with metastatic melanoma harboring an unspecified KIT V559 mutation and a KIT N822I resulted in a complete remission after 6 months and the patient stayed on therapy for 2 years (PMID: 31689840). | 31689840 | |
| KIT T670E | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT T670E in culture (PMID: 35194937). | 35194937 | |
| KIT T670E | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670E demonstrated resistance to Ayvakit (avapritinib) in culture (PMID: 35194937). | 35194937 | |
| KIT T670E | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670E demonstrated resistance to Gleevec (imatinib) in culture (PMID: 35194937). | 35194937 | |
| KIT T670E | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT T670E in culture (PMID: 35194937). | 35194937 | |
| KIT T670E | Advanced Solid Tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670E demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 35194937). | 35194937 | |
| KIT V560D | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Motesanib Diphosphate | Preclinical - Cell culture | Actionable | In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT V560D in culture (PMID: 20633291). | 20633291 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Dasatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D were sensitive to Sprycel (dasatinib) in culture (PMID: 16397263). | 16397263 | |
| KIT V560D | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT V560D demonstrating a partial response and progression free survival of 8.6 months and overall survival of 23.5 months (PMID: 28327988). | 28327988 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D were sensitive to Nexavar (sorafenib) in culture (PMID: 22665524). | 22665524 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased cell viability in transformed cells expressing KIT V560D in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 | |
| KIT V560D | gastrointestinal stromal tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D were sensitive to treatment with Ayvakit (avapritinib) in culture, demonstrating decreased cell growth (PMID: 31270078). | 31270078 | |
| KIT V560D | gastrointestinal stromal tumor | predicted - sensitive | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, Gleevec (imatinib) and Mektovi (binimetinib) combination treatment had manageable toxicity and resulted in a 95% pathological response and 6% RECIST response in a patient with gastrointestinal stromal tumor of the stomach harboring KIT V560D (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT V560D | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Stivarga (regorafineb) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT V560D KIT D820A | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D820A | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) treatment resulted in decreased viability of transformed cells expressing KIT V560D and KIT D820A in culture, but was less effective compared to other treatments (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D820A | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D820A | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D820A | gastrointestinal stromal tumor | resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT D820A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT V560D mutation, who developed resistance to Gleevec (imatinib mesylate) (PMID: 16954519). | 16954519 | |
| KIT V560D KIT D820A | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560D and KIT D820A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 16954519). | 16954519 | |
| KIT V560D KIT D820A | gastrointestinal stromal tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560D and KIT D820A demonstrated resistance to Sutent (sunitinib) in culture (PMID: 18955458). | 18955458 | |
| KIT V560D KIT D820A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D820A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560D KIT V654A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT V654A | Advanced Solid Tumor | sensitive | Motesanib Diphosphate | Preclinical - Cell culture | Actionable | In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/V654A double mutation in culture (PMID: 20633291). | 20633291 | |
| KIT V560D KIT V654A | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated sensitivity to Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560D KIT V654A | Advanced Solid Tumor | resistant | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A were resistant to Flumatinib in culture (PMID: 24205792). | 24205792 | |
| KIT V560D KIT V654A | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT V654A | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT V560D and KIT V654A demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 31270078). | 31270078 | |
| KIT V560D KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D816H | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D816H | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 | |
| KIT V560D KIT D820G KIT N822K KIT Y870* | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT N822K and KIT D820G were identified as secondary resistance mutations in a patient with a gastrointestinal stromal tumor harboring primary KIT Y870* and V560D mutations who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) treatment (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT M552_K558del | gastrointestinal stromal tumor | predicted - resistant | Ponatinib | Case Reports/Case Series | Actionable | In a clinical study, a GIST patient harboring KIT M552_K558del, resistant to multiple tyrosine kinase inhibitors, demonstrated resistance to Iclusig (ponatinib) treatment as indicated by disease progression after 4 weeks of treatment (PMID: 25239608). | 25239608 | |
| KIT V569_L576del KIT V654A KIT N822K | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT V654A and KIT N822K were identified as secondary mutations in a patient with gastrointestinal stromal tumor harboring a primary KIT V569_L576del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 | |
| KIT P551_K558del | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT P551_K558del (reported as K550_W557del) demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT P551_K558del | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT P551_K558del (reported as K550_W557del) demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT P551_K558del | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT P551_K558del (reported as K550_W557del) demonstrated sensitivity to treatment with Stivarga (regorafenib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT P551_K558del | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT P551_K558del (reported as K550_W557del) demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT P551_W557delinsL | gastrointestinal stromal tumor | predicted - sensitive | Ponatinib | Case Reports/Case Series | Actionable | In a clinical study, a GIST patient harboring KIT P551_W557delinsL, resistant to Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib), demonstrated sensitivity to Iclusig (ponatinib) treatment, which resulted in tumor regression and stable disease (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D816G | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D816G | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D816G | Advanced Solid Tumor | resistant | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D816G | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816G were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| ROS1 fusion KIT D816G | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion developed resistance to treatment with Xalkori (crizotinib) and was subsequently found to have acquired KIT D816G (PMID: 29636358). | 29636358 | |
| KIT exon 11 del KIT D816G | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT D816G in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT exon 9 ins KIT D816G | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 9 insertion and KIT D816G in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability and inhibition of KIT signaling (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup | gastrointestinal stromal tumor | predicted - sensitive | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, Gleevec (imatinib) and Mektovi (binimetinib) combination treatment resulted in a 90% pathological response and 27% RECIST response in the primary tumor and 100% pathological response in metastatic lesions of a patient with an esophageal gastrointestinal stromal tumor harboring KIT A502_Y503dup (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT A502_Y503dup | gastrointestinal stromal tumor | predicted - sensitive | M4205 | Preclinical - Pdx | Actionable | In a preclinical study, M4205 treatment inhibited mitosis and decreased tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup (Cancer Res 2022;82(12_Suppl):Abstract nr 2666). | detail... | |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased cell viability and reduced KIT signaling in transformed cells expressing KIT A502_Y503dup in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient derived xenograft (PDX) model with a gastrointestinal stromal tumor harboring KIT A502_Y503dup was sensitive to treatment with Ayvakit (avapritinib), demonstrating a 90% stabilized tumor volume at a dose of 30mg/kg and tumor regression at a dose of 60mg/kg, and inhibition of cell proliferation (PMID: 30274985). | 30274985 | |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) treatment resulted in decreased cell viability and reduced KIT signaling in transformed cells expressing KIT A502_Y503dup in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup | gastrointestinal stromal tumor | predicted - sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) did not significantly inhibit Kit, Erk, or Mtor signaling, but resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). | 29100343 | |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) treatment resulted in decreased viability of transformed cells expressing KIT A502_Y503dup in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT A502_Y503dup demonstrated resistance to treatment with Gleevec (imatinib), resulting in increased tumor volume (PMID: 27777285). | 27777285 | |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Gleevec (imatinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT A502_Y503dup | gastrointestinal stromal tumor | sensitive | Cabozantinib | Preclinical - Pdx | Actionable | In a preclinical study, Cometriq (Cabometyx, cabozantinib) resulted in decreased tumor volume and reduced mitotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT A502_Y503dup (PMID: 27777285). | 27777285 | |
| KIT A502_Y503dup KIT D820E | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal (7.4%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). | 29100343 | |
| KIT A502_Y503dup KIT D820E | gastrointestinal stromal tumor | predicted - resistant | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal (26.2%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). | 29100343 | |
| KIT A502_Y503dup KIT N822K | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT N822K was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT A502_Y503dup mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 | |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Ayvakit (avapritinib) in culture (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated sensitivity to Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 | |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated increased sensitivity to treatment with Ayvakit (avapritinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 | |
| KIT Y672C KIT D816V | Advanced Solid Tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT Y672C demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). | 31270078 | |
| KIT Y672C KIT D816V | Advanced Solid Tumor | decreased response | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT Y672C demonstrated a decreased response compared to cells expressing KIT D816V alone when treated with Rydapt (midostaurin) in culture (PMID: 31270078). | 31270078 | |
| KIT S476I | mast-cell leukemia | predicted - sensitive | Nilotinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, treatment with Tasigna (nilotinib) decreased proliferation of patient-derived neoplastic mast cells harboring KIT S476I in culture (PMID: 25209843). | 25209843 | |
| KIT S476I | mast-cell leukemia | predicted - sensitive | Midostaurin | Preclinical - Patient cell culture | Actionable | In a preclinical study, treatment with Rydapt (midostaurin) decreased proliferation of patient-derived neoplastic mast cells harboring KIT S476I in culture (PMID: 25209843). | 25209843 | |
| KIT K509I | gastrointestinal stromal tumor | no benefit | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in stable disease at 9 months in a patient with advanced gastrointestinal stromal tumor harboring a germline KIT K509I mutation, which was later discontinued due to adverse effects and lack of response (PMID: 23610110). | 23610110 | |
| KIT K509I | mastocytosis | sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in symptom improvements, liver size reduction, and decrease of enzymatic markers in a patient with familial mastocytosis harboring a germline KIT K509I mutation and inhibited growth of white blood cells derived from the patient in culture (PMID: 16183119). | 16183119 | |
| KIT K509I | systemic mastocytosis | sensitive | Dasatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) treatment inhibited growth and induced apoptosis of primary bone marrow mononuclear cells derived from patients with aggressive systemic mastocytosis harboring KIT K509I in culture (PMID: 25139846). | 25139846 | |
| KIT K509I | systemic mastocytosis | sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in symptom and enzymatic improvements in 2 patients with aggressive systemic mastocytosis harboring KIT K509I, with 1 patient achieving a major response/complete remission, and inhibited growth of primary bone marrow mononuclear cells derived from both patients in culture (PMID: 25139846). | 25139846 | |
| KIT K509I | systemic mastocytosis | predicted - sensitive | Midostaurin | Preclinical - Patient cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) treatment inhibited growth but did not induce apoptosis in primary bone marrow mononuclear cells derived from patients with aggressive systemic mastocytosis harboring KIT K509I in culture (PMID: 25139846). | 25139846 | |
| KIT P577_D579del | thymic carcinoma | predicted - sensitive | Sorafenib | Case Reports/Case Series | Actionable | In a clinical case report, a patient with advanced thymic carcinoma harboring KIT P577_D579del demonstrated response to treatment with Nexavar (sorafenib), with a decrease in tumor size (PMID: 20970876). | 20970876 | |
| KIT N505I | melanoma | predicted - sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib) decreased phosphorylation of KIT, AKT, and ERK in melanocytes expressing KIT N505I in culture (PMID: 24317392). | 24317392 | |
| KIT N505I | melanoma | sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, KIT N505I induced phosphorylation of KIT, ERK, and AKT, and was inhibited by Nexavar (sorafenib) in cell culture of melanocytes, demonstrating sensitivity of N505I to sorafenib (PMID: 24317392). | 24317392 | |
| KIT P551_E554del | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Gleevec (imatinib) in culture (PMID: 25239608). | 25239608 | |
| KIT P551_E554del | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT P551_E554del demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT P551_E554del | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Sutent (sunitinib) in culture (PMID: 25239608). | 25239608 | |
| KIT P551_E554del | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT P551_E554del were resistant to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). | 25239608 | |
| KIT act mut | skin melanoma | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org). | detail... | |
| KIT act mut | gastrointestinal stromal tumor | sensitive | Cabozantinib | Preclinical | Actionable | In a preclinical study, Cometriq (cabozantinib) decreased cell viability in imatinib-sensitive and resistant gastrointestinal stromal tumor (GIST) cell lines harboring KIT activating mutations in culture, and induced tumor regression in KIT-mutant GIST mouse models (PMID: 25836719). | 25836719 | |
| KIT act mut | gastrointestinal stromal tumor | not applicable | N/A | Guideline | Diagnostic | KIT activating mutations aid the diagnosis of gastrointestinal stromal tumor (NCCN.org). | detail... | |
| KIT act mut | gastrointestinal stromal tumor | sensitive | Pexidartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX3397 inhibited growth of gastrointestinal stromal tumor cell lines harboring KIT activating mutations in culture and in cell line xenograft models (PMID: 24583793). | 24583793 | |
| KIT act mut | Advanced Solid Tumor | sensitive | PLX9486 | Preclinical | Actionable | In a preclinical study, PLX9486 inhibited KIT mutations, including exon 17 mutations, and demonstrated in vivo and in vitro activity against tumors harboring KIT exon 17 mutations (Cancer Res February 1, 2016 76; IA32). | detail... | |
| KIT K558delinsNP | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing K558delinsNP demonstrated sensitivity to treatment with Stivarga (regorafenib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT K558delinsNP | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing K558delinsNP demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT K558delinsNP | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT K558delinsNP demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT K558delinsNP | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT K558delinsNP demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT D816H | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, KIT D816H demonstrated resistance to Stivarga (regorafenib) in an in vitro assay, and conferred secondary resistance to Stivarga (regorafenib) in transformed cells expressing other KIT mutations (PMID: 25239608). | 25239608 | |
| KIT D816H | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816H were resistant to Gleevec (imatinib) treatment in culture (PMID: 35194937). | 35194937 | |
| KIT D816H | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT D816H demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT D816H | Advanced Solid Tumor | predicted - sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816H were more sensitive to treatment with Sutent (sunitinib) in culture compared to Gleevec (imatinib) (PMID: 24205792). | 24205792 | |
| KIT D816H | Advanced Solid Tumor | predicted - sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816H were more sensitive to treatment with Flumatinib in culture compared to Gleevec (imatinib) (PMID: 24205792). | 24205792 | |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD3229 inhibited growth of cells in culture and tumor growth in a cell line xenograft model of transformed cells expressing KIT W557_K558del and KIT D816H (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | decreased response | Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Gleevec (imatinib) in both culture and xenograft models, resulting in only a slight decrease in tumor volume (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and tumor regression (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | decreased response | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | decreased response | Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in only a slight decrease in tumor volume (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to Ayvakit (avapritinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT exon 11 del KIT D816H | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT D816H in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT D816V | systemic mastocytosis | resistant | Imatinib | FDA contraindicated | Actionable | Gleevec (imatinib) is not indicated for patients with aggressive systemic mastocytosis harboring KIT D816V (FDA.gov). | detail... | |
| KIT D816V | acute myeloid leukemia | sensitive | Cytarabine + Dasatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute myeloid leukemia harboring KIT D816V achieved long-term remission and loss of KIT D816V following treatment with the combination of Sprycel (dasatinib) and Cytosar-U (cytarabine) (PMID: 18986703). | 18986703 | |
| KIT D816V | Advanced Solid Tumor | resistant | Ponatinib | Preclinical | Actionable | In a preclinical study, Iclusig (ponatinib) did not inhibit growth of transformed cells expressing KIT D816V in culture (PMID: 22301675). | 22301675 | |
| KIT D816V | Advanced Solid Tumor | resistant | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were resistant to treatment with Flumatinib in culture (PMID: 24205792). | 24205792 | |
| KIT D816V | acute myeloid leukemia | predicted - sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) demonstrated moderate inhibition of Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | acute myeloid leukemia | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | Advanced Solid Tumor | resistant | Quizartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Quizartinib in culture (PMID: 23497317). | 23497317 | |
| KIT D816V | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited proliferation of transformed cells expressing KIT D816V in culture (PMID: 31085175). | 31085175 | |
| KIT D816V | acute myeloid leukemia | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | hematologic cancer | predicted - sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) demonstrated moderate inhibition of Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | hematologic cancer | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, a mouse myeloid cell line expressing KIT D816V demonstrated resistance to Gleevec (imatinib) in culture (PMID: 12481435). | 12481435 | |
| KIT D816V | hematologic cancer | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were resistant to Stivarga (regorafenib) in culture (PMID: 31085175). | 31085175 | |
| KIT D816V | acute myeloid leukemia | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | Advanced Solid Tumor | predicted - sensitive | BPR1J373 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were sensitive to BPR1J373, demonstrating inhibition of Kit phosphorylation (PMID: 27512117). | 27512117 | |
| KIT D816V | systemic mastocytosis | sensitive | Avapritinib | Phase II | Actionable | In a Phase II trial (PATHFINDER), Ayvakit (avapritinib) treatment resulted in an objective response rate of 75% (24/32) in evaluable patients (pts) with advanced systemic mastocytosis, at 10.4 mo median follow-up, 84% (52/62) of pts remained on study, with median overall survival (OS) not reached, median time to response of 2 mo, an estimated 12 mo OS of 87%, and KIT D816V allele reduction in 53% of pts (33/62) (AACR Annual Meeting, Apr 2021, Abstract CT023; NCT03580655). | detail... | |
| KIT D816V | mast cell neoplasm | predicted - sensitive | Avapritinib | Phase I | Actionable | In a Phase I trial, patients with either aggressive systemic mastocytosis, mast cell leukemia, or systemic mastocytosis with an associated hematologic neoplasm harboring KIT D816V demonstrated a reduction in mast cell burden and a decrease in KIT D816V allelic fraction when treated with Ayvakit (avapritinib) (ASH Annual Meeting, Dec 2017, Plenary 2). | detail... | |
| KIT D816V | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Ayvakit (avapritinib) in culture, demonstrating decreased cell proliferation (PMID: 31270078). | 31270078 | |
| KIT D816V | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) did not inhibit Kit phosphorylation or growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | Advanced Solid Tumor | resistant | Cabozantinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Cometriq (cabozantinib) in culture (PMID: 24205792). | 24205792 | |
| KIT D816V | Advanced Solid Tumor | decreased response | Nilotinib | Preclinical | Actionable | In a preclinical study, Tasigna (nilotinib) decreased viability of cells expressing KIT D816V in culture, but did not inhibit KIT phosphorylation or growth of KIT D816V-expressing tumors in mouse models (PMID: 20442311). | 20442311 | |
| KIT D816V | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) treatment did not inhibit proliferation of transformed cells expressing KIT D816V in culture (PMID: 30523507). | 30523507 | |
| KIT D816V | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Gleevec (imatinib mesylate) in culture (PMID: 15790786). | 15790786 | |
| KIT D816V | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were resistant to Gleevec (imatinib) treatment in culture (PMID: 35194937). | 35194937 | |
| KIT D816V | Advanced Solid Tumor | sensitive | PLX9486 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX9486 treatment inhibited proliferation of Gleevec (imatinib)-resistant transformed cells expressing KIT D816V in culture (PMID: 30523507). | 30523507 | |
| KIT D816V | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were resistant to treatment with Sutent (sunitinib) in culture (PMID: 24205792). | 24205792 | |
| KIT D816V | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, KIT D816V mutations demonstrated resistance to Sutent (sunitinib) in a biochemical assay (PMID: 19164557). | 19164557 | |
| KIT D816V | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | Advanced Solid Tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078). | 31270078 | |
| KIT D816V | hematologic cancer | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Sprycel (dasatinib) in culture, demonstrating reduced cell survival (PMID: 31182436). | 31182436 | |
| KIT D816V | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) did not inhibit Kit phosphorylation or growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | hematologic cancer | sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, FF-10101, as compared to Quizartinib, inhibited cell proliferation of transformed 32Dcl3 murine myeloid cells expressing human Kit D816V (PMID: 29187377). | 29187377 | |
| KIT D816V | systemic mastocytosis | not applicable | N/A | Guideline | Prognostic | KIT D816V is associated with an adverse prognosis in patients with systemic mastocytosis (NCCN.org). | detail... | |
| KIT D816V | systemic mastocytosis | not applicable | N/A | Guideline | Diagnostic | KIT D816V aids in the diagnosis of systemic mastocytosis (NCCN.org). | detail... | |
| KIT D816V | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematopoietic cells expressing KIT D816V demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 17229632). | 17229632 | |
| KIT D816V | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) did not inhibit Kit phosphorylation or growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT D816V | acute myeloid leukemia | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) did not inhibit Kit phosphorylation or growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 | |
| KIT V560G KIT D816V | mast cell neoplasm | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited proliferation of mast cells harboring KIT D816V and KIT V560G in culture (PMID: 31085175). | 31085175 | |
| KIT V560G KIT D816V | mast cell neoplasm | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, mast cells harboring both KIT D816V and KIT V560G were resistant to Sutent (sunitinib) in culture (PMID: 31085175). | 31085175 | |
| KIT V560G KIT D816V | mast-cell leukemia | sensitive | BPR1J373 | Preclinical - Cell culture | Actionable | In a preclinical study, a mast-cell leukemia cell line simultaneously harboring KIT D816V and KIT V560G was sensitive to BPR1J373 in culture, demonstrating inhibition of Kit phosphorylation and apoptotic activity (PMID: 27512117). | 27512117 | |
| KIT V560G KIT D816V | mast-cell leukemia | sensitive | Dasatinib | Preclinical | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis in a mast-cell leukemia cell line harboring both KIT V560G and KIT D816V in culture (PMID: 18024392). | 18024392 | |
| KIT V560G KIT D816V | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560G and D816V demonstrated resistance to Gleevec (imatinib) treatment in culture (PMID: 30523507). | 30523507 | |
| KIT V560G KIT D816V | mast-cell leukemia | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited growth of a human mast cell line harboring both KIT V560G and KIT D816V in culture (PMID: 24552773). | 24552773 | |
| KIT V560G KIT D816V | mast cell neoplasm | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of mast cells harboring KIT D816V and KIT V560G in culture (PMID: 31085175). | 31085175 | |
| KIT V560G KIT D816V | mast cell neoplasm | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, mast cells harboring both KIT D816V and KIT V560G were resistant to Stivarga (regorafenib) in culture (PMID: 31085175). | 31085175 | |
| KIT V560G KIT D816V | mast-cell leukemia | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and proliferation of a mast cell leukemia cell line harboring KIT D816V and V560G in culture (PMID: 29093181). | 29093181 | |
| KIT V560G KIT D816V | mast cell neoplasm | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, mast cells harboring both KIT D816V and KIT V560G were resistant to Gleevec (imatinib) in culture (PMID: 31085175). | 31085175 | |
| KIT V560G KIT D816V | mast cell neoplasm | resistant | Quizartinib | Preclinical | Actionable | In a preclinical study, KIT D816V conferred resistance to Quizartinib in a mast cell line harboring both KIT V560G and KIT D816V in culture (PMID: 23497317). | 23497317 | |
| KIT V560G KIT D816V | Advanced Solid Tumor | sensitive | PLX9486 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX9486 treatment inhibited proliferation of Gleevec (imatinib)-resistant transformed cells expressing KIT V560G and D816V in culture (PMID: 30523507). | 30523507 | |
| KIT V560G KIT D816V | mast cell neoplasm | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited proliferation of mast cells harboring KIT D816V and KIT V560G in culture, and inhibited tumor growth in cell line xenograft models (PMID: 31085175). | 31085175 | |
| KIT D816V NRAS Q61R | melanoma | no benefit | Pembrolizumab + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring KIT D816V and NRAS Q61R demonstrated progressive disease when treated with a combination of Mekinist (trametinib) and Keytruda (pembrolizumab) (PMID: 28514312). | 28514312 | |
| KIT N655K KIT D816V | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT N655K demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). | 31270078 | |
| KIT N655K KIT D816V | Advanced Solid Tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT N655K demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). | 31270078 | |
| KIT D677N KIT D816V | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT D677N demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). | 31270078 | |
| KIT D677N KIT D816V | Advanced Solid Tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT D677N demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). | 31270078 | |
| KIT V654A KIT D816V | Advanced Solid Tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). | 31270078 | |
| KIT V654A KIT D816V | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). | 31270078 | |
| KIT T670V KIT D816V | Advanced Solid Tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670V were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078). | 31270078 | |
| KIT T670V KIT D816V | Advanced Solid Tumor | predicted - resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670V demonstrated some resistance to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). | 31270078 | |
| KIT T670A KIT D816V | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670A demonstrated sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). | 31270078 | |
| KIT T670A KIT D816V | Advanced Solid Tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670A were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078). | 31270078 | |
| KIT exon17 | mucosal melanoma | predicted - sensitive | Avapritinib | Case Reports/Case Series | Actionable | In a clinical case study, Ayvakit (avapritinib) resulted in a reduction of the metastatic lesions, including brain metastases, in a patient with mucosal melanoma harboring a KIT exon 17 mutation (PMID: 35820244). | 35820244 | |
| KIT exon17 | gastrointestinal stromal tumor | predicted - sensitive | Pexidartinib + PLX9486 | Phase I | Actionable | In a Phase I trial, PLX9486 and Pexidartinib (PLX3397) combination therapy demonstrated safety and preliminary efficacy, resulted in a partial response rate of 8.3% (1/12) and progression-free survival not yet reached in patients with advanced solid tumors, 11 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). | detail... | |
| KIT exon17 | gastrointestinal stromal tumor | predicted - sensitive | PLX9486 | Phase I | Actionable | In a Phase I trial, PLX9486 demonstrated safety and preliminary efficacy, resulted in a progression-free survival of more than 24 weeks and partial response in 8.3% (2/24) of patients with advanced solid tumors, 20 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). | detail... | |
| KIT exon17 | gastrointestinal stromal tumor | sensitive | Avapritinib | Phase I | Actionable | In a Phase I trial, Ayvakit (avapritinib) demonstrated preliminary antitumor activity in gastrointestinal stromal tumor patients harboring KIT mutations, with reduced tumor burden in 38% (5/13) of patients, including 1 partial response and 4 stable diseases, and 3 of the 5 responding patients harbored KIT exon 17 mutations (EORTC-NCI-AACR 2016, Abs 6LBA). | detail... | |
| KIT exon17 | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and proliferation of various tumor cell lines harboring KIT exon 17 mutations in culture, and induced tumor regression in an allograft animal model (PMID: 29093181). | 29093181 | |
| KIT exon11 KIT exon17 | gastrointestinal stromal tumor | predicted - sensitive | PLX9486 | Phase I | Actionable | In a Phase I trial, PLX9486 treatment resulted in partial response with 33% decrease of tumor size after 4 cycles of therapy in a patient with gastrointestinal stromal tumor harboring a primary KIT exon 11 mutation and a secondary KIT exon 17 mutation, who progressed on prior Gleevec (imatinib mesylate) and Sutent (sunitinib) therapies (CTOS Annual Meeting, Nov 2017, abstract # 2771952). | detail... | |
| KIT Y553S KIT W557_Q575del KIT D820Y | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT D820Y was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring primary KIT W557_Q575del (reported as Q556_T574del) and KIT Y553S mutations, who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V559D in culture (PMID: 31205508). | 31205508 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT V559D in culture (PMID: 35194937). | 35194937 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D were sensitive to Sutent (sunitinib), demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). | 24205792 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V559D in culture (PMID: 35194937). | 35194937 | |
| KIT V559D | gastrointestinal stromal tumor | predicted - sensitive | Nintedanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of patient-derived gastrointestinal stromal tumor cells harboring KIT V559D in culture (PMID: 35194937). | 35194937 | |
| KIT V559D | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT V559D demonstrating a partial response and progression free survival of 28.3 months and overall survival of 28.3 months (PMID: 28327988). | 28327988 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D were sensitive to Flumatinib, demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). | 24205792 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) decreased KIT signaling, and inhibited growth and induced apoptosis of transformed cells expressing KIT V559D in culture (PMID: 21689725). | 21689725 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) decreased KIT signaling, and inhibited growth and induced apoptosis of transformed cells expressing KIT V559D in culture (PMID: 21689725). | 21689725 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited proliferation of transformed cells expressing KIT V559D in culture (PMID: 35194937). | 35194937 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D were sensitive to Gleevec (imatinib), demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). | 24205792 | |
| KIT V559D | gastrointestinal stromal tumor | sensitive | Axitinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited proliferation of gastrointestinal stromal tumor patient-derived primary cells harboring KIT V559D in culture (PMID: 31205508). | 31205508 | |
| KIT V559D | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT V559D demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT V559D KIT D820Y | Advanced Solid Tumor | sensitive | Nilotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tasigna (nilotinib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture, with increased potency compared to Sprycel (dasatinib) or Nexavar (sorafenib) (PMID: 17699867). | 17699867 | |
| KIT V559D KIT D820Y | Advanced Solid Tumor | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture (PMID: 17699867). | 17699867 | |
| KIT V559D KIT D820Y | Advanced Solid Tumor | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited proliferation of transformed cells expressing a KIT V559D/D820Y double mutation in culture (PMID: 17699867). | 17699867 | |
| KIT V559D KIT V654A | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V654A and KIT V559D in culture (PMID: 31205508). | 31205508 | |
| KIT V559D KIT V654A | Advanced Solid Tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and V654A were resistant to Qinlock (ripretinib) treatment in culture (PMID: 35194937). | 35194937 | |
| KIT V559D KIT V654A | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and V654A were resistant to Ayvakit (avapritinib) treatment in culture (PMID: 35194937). | 35194937 | |
| KIT V559D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT V559D and KIT V654A were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT V559D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V559D and V654A in culture (PMID: 35194937). | 35194937 | |
| KIT V559D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A and KIT V559D in culture (PMID: 31205508). | 31205508 | |
| KIT V559D KIT V654A | Advanced Solid Tumor | predicted - sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D and V654A demonstrated decreased proliferation in response to Ofev (nintedanib) in culture, but were less sensitive to treatment compared to cells expressing either KIT V559D or KIT V654A alone (PMID: 35194937). | 35194937 | |
| KIT V559D KIT N822K | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT N822K and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation and inhibition of Kit, Erk 1/2, and Stat3 phosphorylation (PMID: 24205792). | 24205792 | |
| KIT V559D KIT N822K | Advanced Solid Tumor | no benefit | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT N822K and KIT V559D were insensitive to Sutent (sunitinib) in culture (PMID: 24205792). | 24205792 | |
| KIT V559D KIT Y823D | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical | Actionable | In a preclinical study, Flumatinib treatment in transformed cells co-expressing KIT N822K and KIT V559D demonstrated decreased cell proliferation and inhibition of Kit, Erk 1/2, and Stat3 phosphorylation in culture, and led to improved survival in mouse models (PMID: 24205792). | 24205792 | |
| KIT V559D KIT Y823D | Advanced Solid Tumor | no benefit | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib) treatment in a mouse model with cells expressing KIT V559D and KIT Y823D resulted in shortened survival (PMID: 24205792). | 24205792 | |
| KIT V559D KIT Y823D | Advanced Solid Tumor | no benefit | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT Y823D and KIT V559D were insensitive to Sutent (sunitinib) in culture and in mouse models (PMID: 24205792). | 24205792 | |
| KIT V559D KIT A829P | Advanced Solid Tumor | no benefit | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT A829P and KIT V559D were insensitive to Sutent (sunitinib) in culture (PMID: 24205792). | 24205792 | |
| KIT V559D KIT A829P | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT A829P and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). | 24205792 | |
| KIT V559D KIT D820G | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing KIT D820G and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Cabozantinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cometriq (Cabometyx, cabozantinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del in culture (PMID: 33212994). | 33212994 | |
| KIT W557_K558del | gastrointestinal stromal tumor | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 treatment inhibited Erk phosphorylation and decreased expression of ETV1 and CXCR4 in gastrointestinal stromal tumor cells harboring KIT W557_K558del (PMID: 26936919). | 26936919 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing W557_K558del demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Nilotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tasigna (nilotinib) inhibited growth of transformed cells expressing KIT W557_K558del in culture (PMID: 17699867). | 17699867 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis of transformed cells expressing KIT W557_K558del in culture (PMID: 17699867). | 17699867 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and near complete tumor regression (PMID: 25239608). | 25239608 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 | |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Stivarga (regorafineb) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT V654A, which was established from a patient who did not respond to Gleevec (imatinib) treatment (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ayvakit (avapritinib) failed to inhibit cell growth or KIT signaling in culture and did not suppress tumor growth in cell line xenograft models of transformed cells expressing KIT W557_K558del and KIT V654A (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Pdx | Actionable | In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT V654A, which was established from a patient who did not respond to Gleevec (imatinib) treatment (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Pdx | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and V654A (PMID: 29093181). | 29093181 | |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) failed to reduce cell viability and inhibit KIT signaling in transformed cells expressing KIT W557_K558del and KIT V654A in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with AZD3229 in both culture and cell line xenograft models, resulting in reduced cell viability, decreased KIT signaling, and tumor regression (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | no benefit | Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT Y823D | gastrointestinal stromal tumor | sensitive | PLX9486 | Preclinical - Pdx | Actionable | In a preclinical study, PLX9486 treatment decreased Mapk phosphorylation, inhibited proliferation, and reduced tumor growth and induced regression in a Gleevec (imatinib)-resistant patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and Y823D (PMID: 30523507). | 30523507 | |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT Y823D | gastrointestinal stromal tumor | sensitive | Ponatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, a patient derived GIST cell line co-harboring KIT W557_K558del and KIT Y823D demonstrated sensitivity to Iclusig (ponatinib) in a PDX model, resulting in complete tumor regression (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | predicted - sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated sensitivity to treatment with Stivarga (regorafenib), but was decreased compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT Y823D | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT Y823D | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Pdx | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib mesylate)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and Y823D (PMID: 29093181). | 29093181 | |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT Y823D | gastrointestinal stromal tumor | sensitive | Ripretinib | Preclinical - Pdx | Actionable | In a preclinical study, Qinlock (ripretinib) induced tumor regression in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (PMID: 31085175). | 31085175 | |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT Y823D | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Pdx | Actionable | In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated resistance to Sutent (sunitinb) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A were sensitive to treatment with Stivarga (regorafenib), demonstrating reduced cell viability in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del and KIT D820A in culture, but was less effective compared to other treatments (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A demonstrated resistance to Sutent (sunitinb) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820A were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT D820G | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D820G | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D820G | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT D820G | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D820G were resistant to Sutent (sunitinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Sutent (sunitinb) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K demonstrated resistance to Sutent (sunitinb) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K was sensitive to treatment with Stivarga (regorafenib), demonstrating decreased cell viability in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del and KIT N822K in culture, but was less effective compared to other treatments (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT N822K | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT N822K was identified as a secondary resistance mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT W557_K558del mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT N822K were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del and KIT A829P in culture, but was less effective compared to other treatments (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated resistance to Sutent (sunitinb) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Sutent (sunitinb) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P were sensitive to treatment with Stivarga (regorafenib), but demonstrated a decreased response compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 | |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT Y823D | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT Y823D in culture (PMID: 35194937). | 35194937 | |
| KIT Y823D | Advanced Solid Tumor | sensitive | Motesanib Diphosphate | Preclinical - Cell culture | Actionable | In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT Y823D in culture (PMID: 20633291). | 20633291 | |
| KIT exon 11 del KIT Y823D | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT Y823D in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT positive | breast cancer | predicted - sensitive | Imatinib + Letrozole | Phase 0 | Actionable | In a pilot trial, Gleevec (imatinib mesylate) and Femara (letrozole) combination treatment resulted in clinical partial response in 90% (9/10) and stable disease in 10% (1/10) of the evaluable patients with invasive hormone-sensitive breast cancer, 8 of the 13 enrolled patients had KIT-positive tumors (PMID: 18248884). | 18248884 | |
| KIT positive | prostate neuroendocrine neoplasm | no benefit | Imatinib | Preclinical | Actionable | In a preclinical study, a prostate neuroendocrine tumor mouse model expressing Kit did not respond to Gleevec (imatinib), a result of impaired signaling of the Kit pathway (PMID: 27980106). | 27980106 | |
| KIT positive | germ cell cancer | resistant | Imatinib | Phase II | Actionable | In a small Phase II study, 18 patients with KIT-positive refractory germ cell tumors treated with Gleevec (imatinib) experienced no significant antitumor activity (PMID: 16462496). | 16462496 | |
| KIT positive | gastrointestinal stromal tumor | sensitive | Imatinib | FDA approved | Actionable | In a Phase II trial that supported FDA approval, treatment with Gleevec (imatinib) resulted in an overall response rate of 38% (56/147) and a median duration of response of 13 weeks in patients with metastatic or unresectable KIT-positive GIST (PMID: 12374669). | 12374669 detail... | |
| KIT E562_L576del KIT N822Y | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT N822Y was identified as a secondary mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT E562_L576del mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT T417_D419delinsI | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T417_D419delinsI were sensitive to treatment with Flumatinib, demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT T417_D419delinsI | Advanced Solid Tumor | conflicting | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation in transformed cells over expressing KIT T417_D419delinsI in culture (PMID: 16015387). | 16015387 | |
| KIT T417_D419delinsI | Advanced Solid Tumor | conflicting | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T417_D419delinsI were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). | 24205792 | |
| KIT T417_D419delinsI | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T417_D419delinsI were sensitive to treatment with Sutent (sunitinib), demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT exon13 | gastrointestinal stromal tumor | sensitive | Imatinib + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a gastrointestinal stromal tumor cell line harboring a KIT exon 13 mutation in culture (PMID: 27370604). | 27370604 | |
| KIT exon13 | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 5% (1/19) and partial response in 21% (4/19) of melanoma patients harboring KIT exon 11 or exon 13 mutations (PMID: 28843487; NCT01168050). | 28843487 | |
| KIT exon13 | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), which included a partial response in 7.7% (1/13) of melanoma patients harboring KIT exon 13 mutations (PMID: 28327988). | 28327988 | |
| KIT exon13 | gastrointestinal stromal tumor | sensitive | Adavosertib + Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Adavosertib (MK-1775) and Ayvakit (avapritinib) synergized to inhibit growth of a gastrointestinal stromal tumor cell line harboring a KIT exon 13 mutation in culture (PMID: 33320833). | 33320833 | |
| KIT C443S | mucosal melanoma | sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with mucosal melanoma harboring KIT C443S demonstrated a substantial response to Gleevec (imatinib) in the first two weeks and then developed progression at 15 weeks (PMID: 25003536). | 25003536 | |
| KIT V560G | mast cell neoplasm | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited proliferation of mast cells harboring KIT V560G in culture (PMID: 31085175). | 31085175 | |
| KIT V560G | mast cell neoplasm | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of mast cells harboring KIT V560G in culture (PMID: 31085175). | 31085175 | |
| KIT V560G | Advanced Solid Tumor | sensitive | Nilotinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560G demonstrated inhibition of cell proliferation and tumor regression both in culture and in vivo when treated with Tasigna (nilotinib) (PMID: 20442311). | 20442311 | |
| KIT V560G | mast cell neoplasm | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited proliferation of mast cells harboring KIT V560G in culture (PMID: 31085175). | 31085175 | |
| KIT V560G | mast cell neoplasm | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited proliferation of mast cells harboring KIT V560G in culture (PMID: 31085175). | 31085175 | |
| KIT V560G | mast cell neoplasm | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited proliferation of mast cells harboring KIT V560G in culture (PMID: 31085175). | 31085175 | |
| KIT V560G | mast-cell leukemia | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and proliferation of mast cell leukemia cells harboring KIT V560G in culture (PMID: 29093181). | 29093181 | |
| KIT V560G | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT V560G demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT V560G | mast cell neoplasm | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of mast cells harboring KIT V560G in culture (PMID: 31085175). | 31085175 | |
| KIT over exp | seminoma | sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) in conjunction with third-line chemotherapy resulted in a complete response in a patient with stage IV chemoresistant pure seminoma with KIT overexpression (PMID: 18751412). | 18751412 | |
| KIT over exp | Advanced Solid Tumor | sensitive | Derazantinib | Preclinical - Cell culture | Actionable | In a preclinical study, Derazantinib (ARQ 087) inhibited growth of transformed cells overexpressing Kit in culture (PMID: 27627808). | 27627808 | |
| KIT V560del KIT over exp | thymic carcinoma | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case report, a patient with metastatic thymic carcinoma harboring KIT V560del with KIT over expression initially demonstrated stable disease and reduction in metastatic lesions following treatment with Gleevec (imatinib), but progressed after 6 months (PMID: 15201427). | 15201427 | |
| KIT N822K | acute myeloid leukemia | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). | 31085175 | |
| KIT N822K | acute myeloid leukemia | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). | 31085175 | |
| KIT N822K | acute myeloid leukemia | sensitive | Ripretinib | Preclinical - Pdx | Actionable | In a preclinical study, Qinlock (ripretinib) induced tumor regression in a patient-derived xenograft (PDX) model of acute myeloid leukemia harboring KIT N822K (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). | detail... | |
| KIT N822K | hematologic cancer | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N822K were sensitive to treatment with Sprycel (dasatinib) in culture, demonstrating reduced cell survival (PMID: 31182436). | 31182436 | |
| KIT N822K | Advanced Solid Tumor | predicted - sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N822K were more sensitive to treatment with Flumatinib in culture compared to Gleevec (imatinib), demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT N822K | acute myeloid leukemia | decreased response | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring KIT N822K demonstrated reduced response to growth inhibition by Gleevec (imatinib) compared to GIST cells harboring KIT exon 11 deletion in culture (PMID: 31085175). | 31085175 | |
| KIT N822K | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, KIT N822K was identified in the tumor of a gastrointestinal stromal tumor patient who was resistant to Gleevec (imatinib) treatment (PMID: 26316776). | 26316776 | |
| KIT N822K | thymus squamous cell carcinoma | predicted - sensitive | Avapritinib | Case Reports/Case Series | Actionable | In a clinical case study, Ayvakit (avapritinib) resulted in stable disease in a patient with thymus squamous cell carcinoma harboring KIT N822K (PMID: 35820244). | 35820244 | |
| KIT N822K | leukemia | sensitive | Ponatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited Kit signaling and viability in leukemia cells harboring KIT N822K in culture (PMID: 21482694). | 21482694 | |
| KIT N822K | mucosal melanoma | predicted - sensitive | Avapritinib | Case Reports/Case Series | Actionable | In a clinical case study, Ayvakit (avapritinib) resulted in a partial response in extracranial lesions and stable disease in the central nervous lesions that lasted for 11 months in a patient with mucosal melanoma harboring KIT N822K (PMID: 35820244). | 35820244 | |
| KIT N822K | Advanced Solid Tumor | predicted - sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N822K were more sensitive to treatment with Sutent (sunitinib) in culture compared to Gleevec (imatinib), demonstrating decreased cell proliferation (PMID: 24205792). | 24205792 | |
| KIT N822K | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N822K were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). | 24205792 | |
| KIT N822K | acute myeloid leukemia | predicted - sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). | 31085175 | |
| KIT N822K | acute myeloid leukemia | predicted - sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, an acute myeloid leukemia cell line harboring KIT N822K demonstrated increased sensitivity to Sutent (sunitinib) compared to cells with wild-type KIT, resulting in increased inhibition of colony formation, and induction of cell-cycle arrest, apoptosis, and autophagy in culture (PMID: 31217744). | 31217744 | |
| KIT N822K | acute myeloid leukemia | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 29093181). | 29093181 | |
| KIT N822K | acute myeloid leukemia | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). | 31085175 | |
| KIT N822K | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N822K were sensitive to treatment with Crenolanib in culture, demonstrating reduced cell survival (PMID: 31182436). | 31182436 | |
| KIT N822K | acute myeloid leukemia | sensitive | BPR1J373 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, an acute myeloid leukemia cell line harboring KIT N822K demonstrated sensitivity to treatment with BPR1J373, showing inhibition of Kit phosphorylation and apoptotic induction in culture, and tumor regression in xenograft models (PMID: 27512117). | 27512117 | |
| KIT W557_K558delinsCE KIT N822K | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT N822K was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT W557_K558delinsCE mutation, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). | 18488160 | |
| KIT K642E KIT N822K | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Pdx | Actionable | In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT K642E and KIT N822K (PMID: 32350132). | 32350132 | |
| KIT K642E KIT N822K | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) suppressed tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT K642E and KIT N822K, but was less potent in comparison to treatment with AZD3229 (PMID: 32350132). | 32350132 | |
| KIT exon 11 del KIT N822K | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT N822K in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient derived xenograft (PDX) model with a gastrointestinal stromal tumor harboring KIT W557Lfs*5, KIT P577del, and KIT D820G was sensitive to treatment with Ayvakit (avapritinib), demonstrating a stabilized tumor volume at a dose of 10mg/kg and 27% tumor regression at a dose of 30mg/kg, a histologic response, and apoptotic activity (PMID: 30274985). | 30274985 | |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | predicted - sensitive | M4205 | Preclinical - Pdx | Actionable | In a preclinical study, M4205 treatment inhibited mitosis and decreased tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (Cancer Res 2022;82(12_Suppl):Abstract nr 2666). | detail... | |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | PLX9486 | Preclinical - Pdx | Actionable | In a preclinical study, PLX9486 treatment decreased Mapk phosphorylation and Kit downstream signaling, inhibited proliferation, and reduced tumor growth in a Gleevec (imatinib)-resistant patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (PMID: 30523507). | 30523507 | |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | Cabozantinib | Preclinical - Pdx | Actionable | In a preclinical study, Cometriq (Cabometyx, cabozantinib) slowed tumor growth and decreased mitotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT mutations, P577del, W557Lfs*5, and D820G (PMID: 27777285). | 27777285 | |
| KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT mutations, P577del, W557Lfs*5, and D820G, demonstrated resistance to treatment with Gleevec (imatinib) (PMID: 27777285). | 27777285 | |
| KIT W557C KIT K558_V560del | gastrointestinal stromal tumor | predicted - sensitive | Ponatinib | Case Reports/Case Series | Actionable | In a clinical study, a GIST patient harboring KIT K558_V560del and KIT W557C, resistant to Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib), demonstrated sensitivity when treated with Iclusig (ponatinib), which resulted in a radiologic response and stabilization for six months (PMID: 25239608). | 25239608 | |
| KIT K558_V560del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT V654A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT K558_V560del mutation, who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 | |
| KIT H697Y | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, Sutent (sunitinib) inhibited growth of transformed cell lines overexpressing KIT H697Y in culture (PMID: 19861435). | 19861435 | |
| KIT H697Y | Advanced Solid Tumor | decreased response | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cell lines overexpressing KIT H697Y demonstrated reduced sensitivity to Gleevec (imatinib mesylate)-induced growth inhibition in culture (PMID: 19861435). | 19861435 | |
| KIT K558_V559del | gastrointestinal stromal tumor | predicted - sensitive | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, Gleevec (imatinib) and Mektovi (binimetinib) combination treatment resulted in a 70% pathological response and 46% RECIST response in a patient with a rectal gastrointestinal stromal tumor harboring KIT K558_V559del (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT exon 11 del KIT D820A | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT D820A in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT neg PDGFRB over exp | breast cancer | no benefit | Imatinib | Phase II | Actionable | In a Phase II trial, Gleevec (imatinib mesylate) treatment demonstrated no clinical activity, resulted in no objective response (0/13) in patients with metastatic breast cancer demonstrating Pdgfrb overexpression and negative Kit expression (PMID: 18515258). | 18515258 | |
| KIT exon 9 ins KIT V654A | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 9 insertion and KIT V654A in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT W557_V559delinsF | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Pdx | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in tumor regression in patient-derived xenograft models of gastrointestinal stromal tumor harboring KIT W557_V559delinsF (PMID: 29093181). | 29093181 | |
| KIT V559G | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited proliferation of transformed cells expressing KIT V559G in culture (PMID: 35194937). | 35194937 | |
| KIT V559G | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V559G in culture (PMID: 31205508). | 31205508 | |
| KIT V559G | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT V559G in culture (PMID: 35194937). | 35194937 | |
| KIT V559G | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V559D in culture (PMID: 35194937). | 35194937 | |
| KIT V560del | gastrointestinal stromal tumor | sensitive | G007-LK + Imatinib | Preclinical | Actionable | In a preclinical study, the combination of G007-LK and Gleevec (imatinib) demonstrated increased anti-tumor activity compared to either agent alone in a mouse model of gastrointestinal stromal tumor expressing Kit V558del (corresponding to human V560del) (PMID: 28611108). | 28611108 | |
| KIT V560del | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib) inhibited growth of transformed cell lines over expressing KIT V560del in culture (PMID: 19861435). | 19861435 | |
| KIT V560del | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, Sutent (sunitinib) inhibited growth of transformed cell lines over expressing KIT V560del in culture (PMID: 19861435). | 19861435 | |
| KIT V560del KIT V654A | Advanced Solid Tumor | sensitive | Nilotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tasigna (nilotinib) inhibited proliferation of transformed cells expressing a KIT V560del/V654A double mutation in culture (PMID: 17699867). | 17699867 | |
| KIT V559A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT V559A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 | |
| KIT V559A | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), including a melanoma patient harboring KIT V559A demonstrating a partial response and progression-free survival of 19.4 months and overall survival of 32.9 months (PMID: 28327988). | 28327988 | |
| KIT V559A | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V559A in culture (PMID: 31205508). | 31205508 | |
| KIT V559A | melanoma | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment in a patient with metastatic melanoma resulted in regression of the lung metastasis, which harbored KIT V559A; however, neither the primary tumor or lymph node metastasis responded, which had wild-type KIT (PMID: 19812602). | 19812602 | |
| KIT C809G | Advanced Solid Tumor | predicted - resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, KIT C809G was resistant to inhibition of phosphorylation by Gleevec (imatinib) in cultured cells (PMID: 16954519). | 16954519 | |
| KIT K642E KIT C809G KIT N822H | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, an acquired KIT C809G mutation was identified in a gastrointestinal stromal tumor (GIST) patient harboring KIT K642E and KIT N822H at the time of progression on Gleevec (imatinib) (PMID: 16954519). | 16954519 | |
| KIT I571_D579dup | Advanced Solid Tumor | predicted - resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Gleevec (imatinib) in culture (PMID: 24205792). | 24205792 | |
| KIT I571_D579dup | Advanced Solid Tumor | predicted - resistant | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Flumatinib in culture (PMID: 24205792). | 24205792 | |
| KIT I571_D579dup | Advanced Solid Tumor | predicted - resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT I571_D579dup (KIT D579_H580insIDPTQLPYD) were moderately resistant to Sutent (sunitinib) in culture (PMID: 24205792). | 24205792 | |
| KIT wild-type | Advanced Solid Tumor | sensitive | PLX9486 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX9486 treatment inhibited proliferation of ligand-stimulated cells expressing wild-type KIT in culture (PMID: 30523507). | 30523507 | |
| KIT wild-type | acute megakaryocytic leukemia | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, KIT wild-type megakaryocytic leukemia cells were less sensitive to Ayvakit (avapritinib) compared to cells harboring KIT mutations in culture (PMID: 29093181). | 29093181 | |
| KIT wild-type | acute myeloid leukemia | sensitive | BPR1J373 | Preclinical - Cell culture | Actionable | In a preclinical study, an acute myeloid leukemia cell line harboring KIT wild-type was sensitive to BPR1J373 in culture, demonstrating apoptotic induction and inhibition of cell proliferation (PMID: 27512117). | 27512117 | |
| KIT P551_V555delinsTL | gastrointestinal stromal tumor | sensitive | Sorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited Erk signaling, induced apoptosis, resulted in tumor growth inhibition in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT P551_V555delinsTL (PMID: 19139124). | 19139124 | |
| KIT mutant | melanoma | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) treatment demonstrated manageable safety and preliminary efficacy in patients with KIT-mutated melanoma, and led to an objective response rate of 23% (6/26, 1 complete and 5 partial responses), a median progression-free survival of 7.3 months, and a median duration of response of 7.4 months (Annals of Oncology 32 (2021): S896-S897; NCT02571036). | detail... | |
| KIT mutant | gastrointestinal stromal tumor | sensitive | Imatinib + Infigratinib | Preclinical - Pdx | Actionable | In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antitumor activity in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT mutations (PMID: 25673643). | 25673643 | |
| KIT mutant | gastrointestinal stromal tumor | predicted - sensitive | Avapritinib | Phase I | Actionable | In a Phase I (NAVIGATOR) trial, Ayvakit (avapritinib) treatment resulted in an objective response rate of 13% (7/52, 7 partial responses) and a disease control rate of 63% (33/52) in patients with KIT-mutant gastrointestinal stromal tumor (The CTOS 2018 Annual Meeting, Nov 14-17, Rome Italy, Paper 012 3027631; NCT02508532). | detail... | |
| KIT mutant | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) demonstrated preliminary safety and efficacy in patients with advanced solid tumors, including KIT-mutant gastrointestinal stromal tumor (GIST), with 1 patient harboring KIT exon 11 and 17 mutations demonstrating a partial response, and 7/7 KIT-mutant GIST patients demonstrating a partial metabolic response (EORTC-NCI-AACR 2016, Abs 7LBA). | detail... | |
| KIT mutant | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) was well tolerated, resulted in an objective response in 11.3% (16/142, 16 partial responses) and stable disease in 61.3% (87/142) of patients with advanced gastrointestinal stromal tumor harboring KIT (exon 11, n=103; exon 9, n=26; other, n=6) or PDGFRA mutations (n=7), with a median progression-free survival of 5.6 months (PMID: 32804590; NCT02571036). | 32804590 | |
| KIT mutant | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 4% (1/25), durable partial response in 16% (4/25), and stable disease in 56% (14/25) of melanoma patients harboring KIT mutations (PMID: 28843487; NCT01168050). | 28843487 | |
| KIT mutant | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment in patients with melanoma harboring KIT mutations resulted in an overall response rate of 26.2% (11/42), which included 11 patients with a partial response, a median duration of response of 7.1 months, and an overall survival of 18 months (PMID: 28327988; NCT01028222). | 28327988 | |
| KIT mutant | gastrointestinal stromal tumor | not applicable | N/A | Clinical Study | Diagnostic | KIT mutations are used in the diagnosis of gastrointestinal stromal tumors (PMID: 25193432, PMID: 26276366, PMID: 25729899). | 25193432 26276366 25729899 | |
| KIT K642E | gastrointestinal stromal tumor | sensitive | Imatinib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 25673643). | 25673643 | |
| KIT K642E | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT K642E demonstrating a partial response and a progression free survival of 5.8 months and overall survival of 18.6 months (PMID: 28327988). | 28327988 | |
| KIT K642E | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited proliferation of gastrointestinal stromal tumor cells harboring KIT K642E in culture (PMID: 21170960). | 21170960 | |
| KIT K642E | gastrointestinal stromal tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line harboring KIT K642E demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). | 25239608 | |
| KIT K642E | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor (GIST) cell line and primary GIST patient-derived cells harboring KIT K642E in culture (PMID: 31205508). | 31205508 | |
| KIT K642E | gastrointestinal stromal tumor | sensitive | Axitinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited phosphorylation of KIT and downstream signaling, reduced proliferation, and induced cell-cycle arrest in a cultured gastrointestinal stromal tumor (GIST) cell line harboring KIT K642E, and inhibited proliferation of primary GIST cells harboring KIT K642E in culture (PMID: 31205508). | 31205508 | |
| KIT K642E | vulvar melanoma | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in partial response in a patient with recurrent vulval melanoma harboring KIT K642E, with reduction of tumor mass by 35% at 12 weeks (PMID: 20372153). | 20372153 | |
| KIT K642E | gastrointestinal stromal tumor | predicted - sensitive | M4205 | Preclinical - Pdx | Actionable | In a preclinical study, M4205 treatment inhibited mitosis and decreased tumor growth in a cell line xenograft model and a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT K642E (Cancer Res 2022;82(12_Suppl):Abstract nr 2666). | detail... | |
| KIT K642E | gastrointestinal stromal tumor | sensitive | Nintedanib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ofev (nintedanib) decreased Kit phosphorylation and downstream signaling, induced cell-cycle arrest and apoptosis, and inhibited proliferation of a gastrointestinal stromal tumor cell line and patient-derived cells harboring KIT K642E in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). | 35194937 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Copanlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Aliqopa (copanlisib) inhibited cell growth and PI3K signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32371592). | 32371592 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Nintedanib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ofev (nintedanib) decreased Kit phosphorylation and downstream signaling, induced cell-cycle arrest and apoptosis, and inhibited proliferation of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). | 35194937 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Imatinib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT V560_Y578del in culture (PMID: 25673643). | 25673643 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD3229 inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited growth of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Copanlisib + Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Aliqopa (copanlisib) and Gleevec (imatinib) demonstrated enhanced cell growth inhibition and increased apoptosis of gastrointestinal stromal tumor cells harboring KIT V560_Y578del in culture and in cell line xenograft models (PMID: 32371592). | 32371592 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Axitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and downstream signaling, reduced proliferation and induced cell-cycle arrest in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). | 31205508 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line harboring KIT V560_Y578del demonstrated sensitivity to Gleevec (imatinib) in culture (PMID: 25239608). | 25239608 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | HQP1351 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, HQP1351 treatment inhibited Kit activity and proliferation of a gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_Y578del in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 31673329). | 31673329 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Ponatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_Y578del demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). | 25239608 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture (PMID: 31205508). | 31205508 | |
| KIT V560_Y578del KIT A829P | gastrointestinal stromal tumor | decreased response | Sunitinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT A829P demonstrated a decreased response to treatment with Sutent (sunitinib) (PMID: 25239608). | 25239608 | |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Gleevec (imatinib) failed to decrease cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and did suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Ripretinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Qinlock (ripretinib) resulted in slight decreases in cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, but failed to suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Avapritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ayvakit (avapritinib) failed to decrease cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and did suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD3229 suppressed Kit signaling and cell growth in culture, and inhibited tumor growth in a cell line xenograft model of gastrointestinal stromal tumor harboring KIT V560_Y578del and KIT V654A (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 | |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sutent (sunitinib) inhibited growth of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 | |
| KIT D816X | systemic mastocytosis | not applicable | N/A | Guideline | Diagnostic | Activating mutations at codon 816 of KIT aid in the diagnosis of systemic mastocytosis (NCCN.org). | detail... | |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines for gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations, as adjuvant therapy for patients with localized disease and as first-line therapy for patients with locally advanced, unresectable, or metastatic disease (PMID: 34560242; ESMO.org). | 34560242 detail... | |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines for patients with gastrointestinal stromal tumor (GIST) harboring KIT exon 9 mutations (NCCN.org). | detail... | |
| KIT exon9 | Advanced Solid Tumor | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, Stivarga (regorafineb) had no effect on transformed cells expressing a KIT exon 9 mutation in culture (PMID: 25239608). | 25239608 | |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Sunitinib | Guideline | Actionable | Sutent (sunitinib) is included in guidelines as second-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | detail... 34560242 | |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Sunitinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, GIST patients with KIT exon 9 mutations showed improved progression-free survival (PFS), overall survival, and objective response rate (ORR) compared to patients with exon 11 mutations, with a median PFS of 12.3 months vs. 7.0 months, and an ORR of 19% (8/42) vs. 6% (9/143) following treatment with Sutent (sunitinib) (PMID: 26772734). | 26772734 | |
| KIT exon9 | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a KIT exon 9 mutation demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT exon9 | gastrointestinal stromal tumor | no benefit | Imatinib + Infigratinib | Phase I | Actionable | In a Phase I trial, Truseltiq (infigratinib) and Gleevec (imatinib) combination therapy resulted in stable disease as best response in 58% (7/12) of patients with advanced gastrointestinal stromal tumor harboring KIT mutations in exon 9 (n=3), exon 11 (n=10), or other (n=3), however, the trial was discontinued due to toxicity concerns (PMID: 30101387). | 30101387 | |
| KIT exon9 | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Guideline | Actionable | Qinlock (ripretinib) is included in guidelines as fourth-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... | |
| KIT exon9 | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) was well tolerated, resulted in an objective response in 11.3% (16/142, 16 partial responses) and stable disease in 61.3% (87/142) of patients with advanced gastrointestinal stromal tumor harboring KIT (n=135) or PDGFRA mutations (n=7), with a median progression-free survival of 5.6 months, 18.3% (26/142) of the patients harbored KIT exon 9 mutations (PMID: 32804590; NCT02571036). | 32804590 | |
| KIT exon9 | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a KIT exon 9 mutation demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 | |
| KIT exon9 | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib) had no effect on transformed cells expressing a KIT exon 9 mutation in culture (PMID: 25239608). | 25239608 | |
| KIT exon9 | gastrointestinal stromal tumor | sensitive | Regorafenib | Guideline | Actionable | Stivarga (regorafenib) is included in guidelines as third-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 9 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... | |
| KIT D820E | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT D820E in culture (PMID: 35194937). | 35194937 | |
| KIT D820E | thymic carcinoma | predicted - sensitive | Sorafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic thymic carcinoma harboring KIT D820E demonstrated a partial response to treatment with Nexavar (sorafenib) (PMID: 19461405). | 19461405 | |
| KIT D820E | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT D820E demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT V560E | gastrointestinal stromal tumor | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, neoadjuvant Gleevec (imatinib) treatment resulted in decreased tumor size with a maximal response at 12 months in a patient with gastrointestinal stromal tumor (GIST) harboring KIT V560E, allowing for surgical resection (PMID: 34250403). | 34250403 | |
| KIT W557R | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT W557R demonstrating a partial response and progression free survival of 35.4 months and overall survival of 35.4 months (PMID: 28327988). | 28327988 | |
| KIT W557R KIT L576P | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient co-harboring KIT L576P and KIT W557R demonstrating a partial response and a progression free survival of 5.3 months and overall survival of 14.7 months when treated with Tasigna (nilotinib) (PMID: 28327988). | 28327988 | |
| KIT D820V | gastrointestinal stromal tumor | predicted - sensitive | Avapritinib | Case Reports/Case Series | Actionable | In a Phase I trial, Ayvakit (avapritinib) treatment resulted in tumor reduction lasting through 15 cycles of treatment in a patient with gastrointestinal stromal tumor harboring KIT D820V, whose disease had progressed on previous Gleevec (imatinib), Sutent (sunitinib), and Stivarga (regorafenib) treatment (PMID: 29093181; NCT02508532). | 29093181 | |
| KIT exon 11 del | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited Kit phosphorylation and proliferation of gastrointestinal stromal tumor cells harboring KIT exon 11 deletion in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del | gastrointestinal stromal tumor | sensitive | Adavosertib + Avapritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Adavosertib (MK-1775) and Ayvakit (avapritinib) demonstrated an additive effect on inhibiting cell growth and inducing apoptosis in gastrointestinal stromal tumor cells harboring a KIT exon 11 deletion in culture, and inhibited tumor growth and led to prolonged survival in cell line xenograft models (PMID: 33320833). | 33320833 | |
| KIT exon 11 del | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and proliferation of gastrointestinal stromal tumor cells harboring KIT exon 11 deletion in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited cell growth and induced cell cycle arrest in gastrointestinal stromal tumor cells harboring a KIT exon 11 deletion in culture, and inhibited tumor growth and led to prolonged survival in cell line xenograft models (PMID: 33320833). | 33320833 | |
| KIT exon 11 del | gastrointestinal stromal tumor | no benefit | Adavosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment resulted in reduced cell viability of gastrointestinal stromal tumor cells harboring a KIT exon 11 deletion in culture, but did not lead to improved tumor growth inhibition or prolonged survival compared to controls in cell line xenograft models (PMID: 33320833). | 33320833 | |
| KIT exon 11 del | gastrointestinal stromal tumor | predicted - sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited Kit phosphorylation and proliferation of gastrointestinal stromal tumor cells harboring KIT exon 11 deletion in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del | gastrointestinal stromal tumor | predicted - sensitive | Imatinib | Phase III | Actionable | In a Phase III trial, gastrointestinal stromal tumor patients harboring KIT exon 11 deletions or indels demonstrated improved recurrence-free survival (RFS) with 3-year adjuvant Gleevec (imatinib) treatment (5-year RFS, 70%), compared to patients receiving 1-year treatment (5-year RFS, 41.3%) (PMID: 28334365). | 28334365 | |
| KIT exon 11 del | gastrointestinal stromal tumor | sensitive | Ripretinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited Kit phosphorylation and proliferation of gastrointestinal stromal tumor cells harboring KIT exon 11 deletion, resulted in tumor regression in cell line xenograft models (PMID: 31085175). | 31085175 | |
| KIT exon 11 del | gastrointestinal stromal tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT exon 11 del | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited Kit phosphorylation and proliferation of gastrointestinal stromal tumor cells harboring KIT exon 11 deletion in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del | gastrointestinal stromal tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited Kit phosphorylation and proliferation of gastrointestinal stromal tumor cells harboring KIT exon 11 deletion in culture (PMID: 31085175). | 31085175 | |
| KIT exon 11 del KIT V654A | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT V654A in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT exon 11 del KIT D820G | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT D820G in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT exon 11 del KIT A829P | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT A829P in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... | |
| KIT V654A | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT V654A demonstrated some sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 31205508). | 31205508 | |
| KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 35194937). | 35194937 | |
| KIT V654A | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 35194937). | 35194937 | |
| KIT V654A | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V654A in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). | 31205508 | |
| KIT V654A | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 16751810). | 16751810 | |
| KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Avapritinib | Phase I | Actionable | In a Phase I trial, patients with gastrointestinal stromal tumors harboring either KIT V654A or KIT T670I demonstrated decreased overall response rate (0%, 0/25 vs. 26%, 22/84) and increased progressive disease rate (72% vs 23%) compared to those without either KIT mutation when treated with Ayvakit (avapritinib) (PMID: 31270078; NCT02508532). | 31270078 | |
| KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) (PMID: 33579785). | 33579785 | |
| KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) demonstrated resistance to treatment with Gleevec (imatinib) (PMID: 33579785). | 33579785 | |
| KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT V560_L576del and V654A with overexpression of GPR20 (IHC score 3+) (PMID: 33579785). | 33579785 | |
| KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_L576del and KIT V654A demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). | 25239608 | |
| KIT V560_L576del KIT V654A | gastrointestinal stromal tumor | sensitive | HQP1351 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, HQP1351 treatment inhibited Kit downstream signalling, resulted in cell cycle arrest and apoptosis in a Gleevec (imatinib)-resistant gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_L576del and V654A in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 31673329). | 31673329 | |
| KIT exon11 KIT V654A | gastrointestinal stromal tumor | sensitive | Copanlisib | Preclinical - Cell culture | Actionable | In a preclinical study, Aliqopa (copanlisib) inhibited cell growth and PI3K signaling in a gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion and KIT V654A in culture (PMID: 32371592). | 32371592 | |
| KIT exon11 KIT V654A | gastrointestinal stromal tumor | sensitive | Imatinib + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 deletion mutation and KIT V654A in culture (PMID: 27370604). | 27370604 | |
| KIT exon11 KIT V654A | gastrointestinal stromal tumor | predicted - sensitive | Copanlisib + Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Aliqopa (copanlisib) and Gleevec (imatinib) demonstrated enhanced cell growth inhibition but did not result in increased apoptosis of gastrointestinal stromal tumor cells harboring a KIT exon 11 deletion and KIT V654A compared to either agent alone in culture (PMID: 32371592). | 32371592 | |
| KIT V559_G565del KIT V654A KIT A829P | gastrointestinal stromal tumor | predicted - sensitive | Ripretinib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with Qinlock (ripretinib) decreased circulating tumor DNA, resulted in stable disease lasting over 26 months in a patient with gastrointestinal stromal tumor harboring a primary KIT V559_G565del mutation and two acquired resistance mutations, KIT V654A and KIT A829P (PMID: 31085175; NCT02571036). | 31085175 | |
| KIT Q556_V559delinsHT KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT V654A was identified as a secondary resistance mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT Q556_V559delinsHT mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT Q556_I571del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, KIT V654A was identified as a secondary mutation in a patient with a gastrointestinal stromal tumor harboring a primary KIT Q556_I571del mutation who developed resistance to Gleevec (imatinib) and Mektovi (binimetinib) (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT V560_L576del | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, a patient derived GIST cell line harboring KIT V560_L576del demonstrated sensitivity to Gleevec (imatinib) in both culture and PDX models, resulting in phosphorylation inhibition of Akt, Kit, and Erk (PMID: 25239608). | 25239608 | |
| KIT V560_L576del | gastrointestinal stromal tumor | sensitive | Ponatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, a patient derived GIST cell line harboring KIT V560_L576del demonstrated sensitivity to Iclusig (ponatinib) in both culture and PDX models, resulting in phosphorylation inhibition of Akt, Kit, and Erk (PMID: 25239608). | 25239608 | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Sunitinib | Guideline | Actionable | Sutent (sunitinib) is included in guidelines as second-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 11 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Sunitinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, Sutent (sunitinib) treatment demonstrated efficacy in gastrointestinal stromal tumor (GIST) patients harboring KIT mutations previously treated with Gleevec (imatinib), and resulted in an objective response rate (ORR) of 6% (9/143) and median progression-free survival (mPFS) of 7.0 months in patients with KIT exon 11 mutations, and ORR of 19% (8/42) and mPFS of 12.3 months in patients with KIT exon 9 mutations (PMID: 26772734; NCT01459757). | 26772734 | |
| KIT exon11 | gastrointestinal stromal tumor | predicted - sensitive | Ponatinib | Phase II | Actionable | In a Phase II trial, Iclusig (ponatinib) treatment resulted in partial response in 7% (2/27), stable disease in 59% (16/27), a median progression free survival of 4.3 months and a median overall survival of 15.0 months in gastrointestinal stromal tumor patients harboring KIT exon 11 mutations after prior tyrosine kinase inhibitor treatment failure (J Clin Oncol 33, 2015 (suppl; abstr 10535)). | detail... | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Imatinib + PKF118-310 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of PKF118-310 and Gleevec (imatinib) resulted in decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations compared to Gleevec (imatinib) alone, in culture (PMID: 28611108). | 28611108 | |
| KIT exon11 | gastrointestinal stromal tumor | predicted - sensitive | Dasatinib | Phase II | Actionable | In a Phase II clinical trial, Sprycel (dasatinib) demonstrated preliminary activity in patients with Gleevec (imatinib)-resistant gastrointestinal stromal tumor (GIST), including patients harboring KIT exon 11 mutations, with a partial response rate of 32% (15/47), median progression-free survival of 2.0 months, and overall survival of 19 months (J Clin Oncol 29: 2011 (suppl; abstr 10006)). | detail... | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines for gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 11 mutations, as adjuvant therapy for patients with localized disease and as first-line therapy for patients with locally advanced, unresectable, or metastatic disease (PMID: 34560242; ESMO.org). | 34560242 detail... | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Imatinib | Phase III | Actionable | In a Phase III trial, a long-term analysis of gastrointestinal stromal tumor (GIST) patients treated with Gleevec (imatinib) demonstrated patients harboring KIT exon 11 mutations had a median progression-free survival of 39.4 months, and median overall survival was not reached, with 69.1% of patients with KIT exon 11 mutations alive at 5 years (PMID: 26687836; NCT00367861). | 26687836 | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Imatinib | Phase III | Actionable | In a Phase III trial, Gleevec (imatinib) treatment resulted in longer overall survival (OS) (66 vs 40 months) in gastrointestinal stromal tumor (GIST) patients harboring KIT exon 11 mutations compared to KIT and PDGFRA wild-type patients, while subtypes of KIT exon 11 mutations (deletion, insertation/duplication, point mutation) did not affect OS outcome (PMID: 28196207; NCT00009906). | 28196207 | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Imatinib | Guideline | Actionable | Gleevec (imatinib) is included in guidelines for patients with gastrointestinal stromal tumor (GIST) harboring KIT exon 11 mutations (NCCN.org). | detail... | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Imatinib + MK2206 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Gleevec (imatinib) and MK2206 increased growth inhibition and decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations in culture, and improved survival and inhibited tumor growth in a KIT exon 11-mutant GIST cell line xenograft model, with increased efficacy compared to either agent alone (PMID: 27370604). | 27370604 | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Ripretinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited Kit phosphorylation and proliferation of gastrointestinal stromal tumor cells harboring a KIT exon 11 deletion mutation in culture, and resulted in tumor regression in cell line xenograft models (PMID: 31085175). | 31085175 | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Ripretinib | Guideline | Actionable | Qinlock (ripretinib) is included in guidelines as fourth-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 11 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Ripretinib | Phase I | Actionable | In a Phase I trial, Qinlock (ripretinib) was well tolerated, resulted in an objective response in 11.3% (16/142, 16 partial responses) and stable disease in 61.3% (87/142) of patients with advanced gastrointestinal stromal tumor harboring KIT (n=135) or PDGFRA mutations (n=7), with a median progression-free survival of 5.6 months, 72.5% (103/142) of the patients harbored KIT exon 11 mutations (PMID: 32804590; NCT02571036). | 32804590 | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Imatinib + XAV939 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of XAV939 and Gleevec (imatinib) resulted in decreased viability of gastrointestinal stromal tumor (GIST) cell lines harboring KIT exon 11 mutations compared to Gleevec (imatinib) alone, in culture (PMID: 28611108). | 28611108 | |
| KIT exon11 | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41), which included a partial response of 38.5% (10/26) and a progression free survival of 5.4 months in melanoma patients harboring KIT exon 11 mutations (PMID: 28327988). | 28327988 | |
| KIT exon11 | melanoma | sensitive | Nilotinib | Phase II | Actionable | In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 5% (1/19) and partial response in 21% (4/19) of melanoma patients harboring KIT exon 11 or exon 13 mutations (PMID: 28843487; NCT01168050). | 28843487 | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Regorafenib | Guideline | Actionable | Stivarga (regorafenib) is included in guidelines as third-line or subsequent therapy for locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) patients harboring sensitizing mutations, such as KIT exon 11 mutations (PMID: 34560242; ESMO.org). | 34560242 detail... | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Regorafenib | Phase II | Actionable | In a Phase II clinical trial, treatment with Stivarga (regorafenib) resulted in a clinical benefit rate of 76% (25/33), a median progression-free survival (PFS) of 13.2 months, and a median overall survival of 25 months in patients with gastrointestinal stromal tumors, with patients with KIT exon 11 mutations demonstrating the longest PFS of 13.4 months (PMID: 27371698). | 27371698 | |
| KIT exon11 | gastrointestinal stromal tumor | sensitive | Nilotinib | Phase III | Actionable | In a Phase III trial, a 24 month progression free survival was observed in 69.6% of advanced GIST patients harboring KIT exon 11 mutations when treated with Tasigna (nilotinib) (J Clin Oncol May 2013 vol. 31 no. 15_suppl 10501). | detail... | |
| KIT exon11 | melanoma | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in a partial response in a patient with metastastic anal melanoma harboring a 21 base-pair duplication in KIT exon 11, and reduced pulmonary metastasis by 60% (PMID: 20372153). | 20372153 | |
| KIT exon11 | gastrointestinal stromal tumor | no benefit | Imatinib + Infigratinib | Phase I | Actionable | In a Phase I trial, Truseltiq (infigratinib) and Gleevec (imatinib) combination therapy resulted in stable disease as best response in 58% (7/12) of patients with advanced gastrointestinal stromal tumor harboring KIT mutations in exon 11 (n=10), exon 9 (n=3), or other (n=3), however, the trial was discontinued due to toxicity concerns (PMID: 30101387). | 30101387 | |
| KIT exon11 | gastrointestinal stromal tumor | predicted - sensitive | Pexidartinib + PLX9486 | Phase I | Actionable | In a Phase I trial, PLX9486 and Pexidartinib (PLX3397) combination therapy demonstrated safety and preliminary efficacy, resulted in a partial response rate of 8.3% (1/12) and progression-free survival not yet reached in patients with advanced solid tumors, 11 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). | detail... | |
| KIT exon11 | gastrointestinal stromal tumor | predicted - sensitive | PLX9486 | Phase I | Actionable | In a Phase I trial, PLX9486 demonstrated safety and preliminary efficacy, resulted in a progression-free survival of more than 24 weeks and partial response in 8.3% (2/24) of patients with advanced solid tumors, 20 of these patients had gastrointestinal stromal tumor that progressed on Gleevec (imatinib mesylate), and most harbored KIT exon 11 and exon 17 mutations (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 11509-11509; NCT02401815). | detail... | |
| KIT exon11 KIT A829P | gastrointestinal stromal tumor | sensitive | Imatinib + MK2206 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 mutation and KIT A829P in culture (PMID: 27370604). | 27370604 | |
| KIT D820Y | melanoma | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib mesylate) failed to inhibit MNK pathway activation and proliferation of melanoma cell lines harboring KIT D820Y in culture (PMID: 29035277). | 29035277 | |
| KIT D820Y | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT D820Y in culture (PMID: 35194937). | 35194937 | |
| KIT D820Y | melanoma | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT D820Y in culture (PMID: 29035277). | 29035277 | |
| KIT D820Y | melanoma | sensitive | SEL201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cell lines harboring KIT D820Y in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). | 29035277 | |
| KIT D820Y | melanoma | predicted - sensitive | Sorafenib | Case Reports/Case Series | Actionable | In a clinical case study, Nexavar (sorafenib) treatment resulted in stable disease with 27% reduction in target lesions at 4 weeks in a patient with anal melanoma and pulmonary metastases harboring KIT D820Y (PMID: 20372153). | 20372153 | |
| KIT Y553N | thymic carcinoma | sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic thymic carcinoma harboring KIT Y553N demonstrated improved clinical performance and reduction in metastatic lesions following treatment with Gleevec (imatinib) (PMID: 21969494). | 21969494 | |
| KIT D419G | hematologic cancer | no benefit | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing KIT D419G did not respond to treatment with Crenolanib in culture (PMID: 31182436). | 31182436 | |
| KIT D419G | hematologic cancer | no benefit | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing KIT D419G did not respond to treatment with Sprycel (dasatinib) in culture (PMID: 31182436). | 31182436 | |
| KIT D419del | mastocytosis | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resolved symptoms and stopped disease progression after 32 months in a pediatric patient with progressive cutaneous mastocytosis harboring a somatic KIT D419del and a germline S840N mutation (PMID: 18567837). | 18567837 | |
| KIT D419del | Advanced Solid Tumor | predicted - sensitive | Imatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Gleevec (imatinib) treatment inhibited Kit autophosphorylation in transformed cells expressing KIT D419del in culture (PMID: 16143141). | 16143141 | |
| KIT D419del | hematologic cancer | no benefit | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing KIT D419del did not respond to treatment with Crenolanib in culture (PMID: 31182436). | 31182436 | |
| KIT D419del | hematologic cancer | no benefit | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing KIT D419del did not respond to treatment with Sprycel (dasatinib) in culture (PMID: 31182436). | 31182436 | |
| KIT D579del | thymic carcinoma | sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with thymic carcinoma harboring KIT D579del achieved disease stabilization following treatment with Gleevec (imatinib) (PMID: 24419427). | 24419427 | |
| KIT A829P | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT A829P demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 | |
| KIT A829P | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT A829P in culture (PMID: 35194937). | 35194937 | |
| KIT A829P | melanoma | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing KIT A829P demonstrated resistance to treatment with Sutent (sunitinib) (PMID: 23582185, PMID: 25594040). | 23582185 25594040 | |
| KIT A829P | melanoma | sensitive | Dasatinib | Preclinical | Actionable | In a preclinical study, Sprycel (dasatinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT A829P (PMID: 23582185, PMID: 25594040). | 23582185 25594040 | |
| KIT A829P | melanoma | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing KIT A829P demonstrated resistance to treatment with Gleevec (imatinib mesylate) (PMID: 23582185, PMID: 25594040). | 23582185 25594040 | |
| KIT A829P | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT A829P in culture, however, with decreased potency compared to its potency against other KIT variants (PMID: 31205508). | 31205508 | |
| KIT A829P | melanoma | sensitive | Nilotinib | Preclinical | Actionable | In a preclinical study, Tasigna (nilotinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT A829P (PMID: 23582185, PMID: 25594040). | 23582185 25594040 | |
| KIT M552_V559del | Advanced Solid Tumor | sensitive | Motesanib Diphosphate | Preclinical - Cell culture | Actionable | In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT M552_V559del in culture (PMID: 20633291). | 20633291 | |
| KIT D816F | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816F were resistant to Gleevec (imatinib mesylate) in culture (PMID: 16397263). | 16397263 | |
| KIT E562_L576del | gastrointestinal stromal tumor | predicted - sensitive | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, Gleevec (imatinib) and Mektovi (binimetinib) combination treatment resulted in an 80% pathological response and 23% RECIST response in a patient with a small bowel gastrointestinal stromal tumor harboring KIT E562_L576del (PMID: 35041493; NCT01991379). | 35041493 | |
| KIT N655K | gastrointestinal stromal tumor | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with gastrointestinal stromal tumor (GIST) harboring a germline KIT N655K mutation, associated with hereditary GIST syndrome, demonstrated slow disease progression for 12 months while on treatment with Gleevec (imatinib) at 400mg/d, and upon disease progression following surgery and 15 months of Sutent (sunitinib) treatment, was rechallenged with Gleevec (imatinib) at 800mg/d and remained stable for a further 9 months (PMID: 33212994). | 33212994 | |
| KIT N655K | Advanced Solid Tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Ayvakit (avapritinib) in culture, but were less sensitive than cells expressing KIT W557_K558del (PMID: 33212994). | 33212994 | |
| KIT N655K | Advanced Solid Tumor | predicted - sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Gleevec (imatinib) treatment in culture, resulting in reduced cell viability at high treatment dosages (PMID: 33212994). | 33212994 | |
| KIT N655K | Advanced Solid Tumor | predicted - sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Qinlock (ripretinib) treatment in culture, but were less sensitive than cells expressing KIT W557_K558del (PMID: 33212994). | 33212994 | |
| KIT N655K | Advanced Solid Tumor | decreased response | Cabozantinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Cometriq (Cabometyx, cabozantinib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). | 33212994 | |
| KIT N655K | Advanced Solid Tumor | decreased response | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Sutent (sunitinib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). | 33212994 | |
| KIT N655K | Advanced Solid Tumor | decreased response | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Stivarga (regorafenib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). | 33212994 | |
| KIT D820N | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT D820N was identified as a secondary mutation in the metastatic lesions from a gastrointestinal stromal tumor patient whose disease progressed on Gleevec (imatinib) (PMID: 18628470). | 18628470 | |
| KIT V559_V560del | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Gleevec (imatinib), demonstrating decreased cell proliferation in culture (PMID: 24205792). | 24205792 | |
| KIT V559_V560del | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Flumatinib, demonstrating decreased cell proliferation in culture (PMID: 24205792). | 24205792 | |
| KIT V559_V560del | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559_V560del were sensitive to Sutent (sunitinib), demonstrating decreased cell proliferation in culture (PMID: 24205792). | 24205792 | |
| KIT M541L | chronic leukemia | sensitive | Imatinib | Phase I | Actionable | In Phase I trials, KIT M541L has been associated with response to Gleevec (imatinib) in chronic eosinophilic leukemia, NOS (PMID: 25015329) and mastocytosis (PMID: 18795925). | 25015329 18795925 | |
| ALK fusion ALK G1202R KIT amp | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK G1202R secondary mutation as well as KIT amplification were identified in a patient with ALK fusion-positive non-small cell lung cancer with resistance to Xalkori (crizotinib) (PMID: 22277784). | 22277784 | |
| KIT P551_V555del | gastrointestinal stromal tumor | sensitive | Sorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited Erk signaling, induced apoptosis, resulted in tumor growth inhibition in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT P551_V555del (PMID: 19139124). | 19139124 | |
| KIT F522C | systemic mastocytosis | sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in symptom and pathologic improvements in a patient with systemic mastocytosis harboring germline KIT F522C and inhibited growth of primary bone marrow cells derived from the patient in culture (PMID: 15070706). | 15070706 | |
| KIT W557G | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, Gleevec (imatinib mesylate) inhibited Kit phosphorylation efficiently in transformed human cells over expressing KIT W557G in culture (PMID: 23567324). | 23567324 | |
| KIT W557G | extraskeletal myxoid chondrosarcoma | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in stable disease lasting at least 3 years in a patient with extraskeletal myxoid chondrosarcoma harboring KIT W557G (PMID: 34446510). | 34446510 | |
| KIT D820G | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT D820G in culture (PMID: 35194937). | 35194937 | |
| KIT T632I | melanoma | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in worsened condition and continued disease progression and metastasis in a patient with metastatic melanoma harboring KIT T632I (PMID: 31043947). | 31043947 | |
| KIT L576P | melanoma | unknown | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in initial tumor reduction, but was followed by disease progression at all tumor sites in a patient with metastasized labial melanoma harboring KIT L576P (PMID: 20372153). | 20372153 | |
| KIT L576P | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including three melanoma patients harboring KIT L576P demonstrating a partial response (PMID: 28327988). | 28327988 | |
| KIT L576P | melanoma | sensitive | SEL201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cells harboring KIT L576P in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). | 29035277 | |
| KIT L576P | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). | 35194937 | |
| KIT L576P | melanoma | predicted - sensitive | Bevacizumab + Sorafenib | Case Reports/Case Series | Actionable | In a Phase I trial, a melanoma patient harboring KIT L576P demonstrated sensitivity to the combination treatment of Nexavar (sorafenib) and Avastin (bevacizumab), resulting in a partial response for 8 months (PMID: 25363205). | 25363205 | |
| KIT L576P | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). | 35194937 | |
| KIT L576P | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT L576P in culture (PMID: 31205508). | 31205508 | |
| KIT L576P | melanoma | sensitive | Dasatinib | Case Reports/Case Series | Actionable | In a clinical study, two patients with melanoma harboring KIT L576P, one who had progressed on Gleevec (imatinib), demonstrated initial clinical benefit following treatment with Sprycel (dasatinib); however, one patient progressed after 3 months, and the other patient progressed after 4 months of treatment (PMID: 19671763). | 19671763 | |
| KIT L576P | melanoma | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT L576P in culture (PMID: 29035277). | 29035277 | |
| KIT L576P | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). | 35194937 | |
| KIT W557_E561del | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_E561del with overexpression of GPR20 (IHC score 3+) (PMID: 33579785). | 33579785 | |
| KIT W557_E561del | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_E561del with overexpression of GPR20 (IHC score 3+) (PMID: 33579785). | 33579785 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|