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Profile Name | KIT Y823D |
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 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 | 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 | 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 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 Y823D | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical | Actionable | In a preclinical study, Flumatinib treatment in transformed cells co-expressing KIT Y823D and KIT V559D resulted in decreased cell proliferation and inhibition of Kit, Erk1/2, 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 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 | 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 | 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 | 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 | 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 | 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 (sunitinib) in culture (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 | 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 | 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 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 W557_K558del KIT Y823D | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, two patients with gastrointestinal stromal tumors harboring KIT W557_K558del progressed following an initial response to Gleevec (imatinib), and were found to have acquired the secondary resistance mutation KIT Y823D in one lesion (PMID: 18294292). | 18294292 |
KIT P551I KIT M552_V559del KIT Y823D | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with gastrointestinal stromal tumor harboring KIT M552_V559del and KIT P551I progressed following an initial response to Gleevec (imatinib), and was found to have acquired the secondary resistance mutation KIT Y823D (PMID: 18294292). | 18294292 |