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Profile Name | KIT W557_K558del KIT Y823D |
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 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 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 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 |