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Profile Name | KIT A502_Y503dup |
Gene Variant Detail | |
Relevant Treatment Approaches | KIT Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
KIT A502_Y503dup | gastrointestinal stromal tumor | conflicting | KIT Inhibitor | 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 | gastrointestinal stromal tumor | sensitive | KIT Inhibitor | 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 | Advanced Solid Tumor | sensitive | KIT Inhibitor | 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 | Advanced Solid Tumor | sensitive | KIT Inhibitor | 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 | Advanced Solid Tumor | sensitive | KIT Inhibitor | 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 | gastrointestinal stromal tumor | predicted - sensitive | KIT Inhibitor | 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 | gastrointestinal stromal tumor | sensitive | KIT Inhibitor | 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 | KIT Inhibitor | 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 | Advanced Solid Tumor | sensitive | KIT Inhibitor | 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 | Advanced Solid Tumor | sensitive | KIT Inhibitor | 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 | Advanced Solid Tumor | sensitive | KIT Inhibitor | 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 | KIT Inhibitor | 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 | gastrointestinal stromal tumor | predicted - sensitive | KIT Inhibitor | IDRX-42 | Preclinical - Pdx | Actionable | In a preclinical study, IDRX-42 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 | gastrointestinal stromal tumor | conflicting | KIT Inhibitor | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib) treatment stabilized tumor growth in a gastrointestinal stromal tumor patient-derived xenograft (PDX) model harboring KIT A502_Y503dup (PMID: 35625872). | 35625872 |
KIT A502_Y503dup | gastrointestinal stromal tumor | predicted - sensitive | KIT Inhibitor | Binimetinib + Dovitinib | Preclinical - Pdx | Actionable | In preclinical study, combination treatment with Mektovi (binimetinib) and Dovitinib (TKI258) resulted in tumor shrinkage in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup (PMID: 35625872). | 35625872 |
KIT A502_Y503dup | gastrointestinal stromal tumor | predicted - sensitive | KIT Inhibitor | Dovitinib | Preclinical - Pdx | Actionable | In preclinical study, Dovitinib (TKI258) treatment resulted in tumor shrinkage in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup (PMID: 35625872). | 35625872 |
KIT A502_Y503dup | gastrointestinal stromal tumor | resistant | KIT Inhibitor | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, a gastrointestinal stromal tumor cell line expressing KIT A502_Y503dup demonstrated resistance to Qinlock (ripretinib) in culture (PMID: 38408285). | 38408285 |
KIT A502_Y503dup | gastrointestinal stromal tumor | sensitive | KIT Inhibitor | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited viability of a gastrointestinal stromal tumor cell line harboring KIT A502_Y503dup in culture (PMID: 38408285). | 38408285 |
KIT A502_Y503dup | gastrointestinal stromal tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited viability of a gastrointestinal stromal tumor cell line harboring KIT A502_Y503dup in culture (PMID: 38408285). | 38408285 |