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Profile Name | KIT T670I |
Gene Variant Detail | |
Relevant Treatment Approaches | KIT Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 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 | 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 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 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 | 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 | 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 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 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 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 | 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 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 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 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 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 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 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 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 | 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 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 | 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 T670I in culture (PMID: 31085175). | 31085175 |
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 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 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 | 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 | 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 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 | 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 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 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 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 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 | 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 | 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 W557_K558del KIT T670I | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with gastrointestinal stromal tumor harboring KIT W557_K558del progressed following an initial response to Gleevec (imatinib), and was found to have acquired the secondary resistance mutation KIT T670I (PMID: 18294292). | 18294292 |
CTNNB1 mut KIT V559D KIT T670I | hepatocellular carcinoma | predicted - sensitive | WNTinib | Preclinical - Cell culture | Actionable | In a preclinical study, a hepatocellular carcinoma cell line harboring a deletion of CTNNB1 exons and expressing KIT V559D and T670I was resistant to WNTinib in culture (PMID: 37537299). | 37537299 |