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Molecular Profile Detail

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Profile Name KIT A502_Y503dup
Gene Variant Detail

KIT A502_Y503dup (gain of function)

Relevant Treatment Approaches KIT Inhibitor

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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