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Profile Name RET C634R
Gene Variant Detail

RET C634R (gain of function)

Relevant Treatment Approaches RET Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased growth of cells expressing RET C634R in culture (PMID: 17664273). 17664273
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, transformed human cell lines expressing RET C634R demonstrated sensitivity to Iclusig (ponatinib) (PMID: 23811235). 23811235
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET kinase activity and proliferation in transformed cells expressing RET C634R in culture (PMID: 16507829). 16507829
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited RET phosphorylation and decreased growth of transformed cells expressing RET C634R in culture (PMID: 15184865). 15184865
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Pz-1 Preclinical - Cell line xenograft Actionable In a preclinical study, Pz-1 inhibited Ret signaling in transformed cells over expressing RET C634R and inhibited tumor growth in cell line xenografts models (PMID: 26126987). 26126987
RET C634R medullary thyroid carcinoma predicted - sensitive RET Inhibitor Sorafenib Case Reports/Case Series Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in a partial response in 1 and stable disease in another patient with medullary thyroid carcinoma harboring RET C634R (PMID: 20368568; NCT00390325). 20368568
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Pz-1 Preclinical - Cell culture Actionable In a preclinical study, Pz-1 treatment inhibited Ret phosphorylation and growth of transformed cells expressing RET C634R in culture (PMID: 34373541). 34373541
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling and viability in transformed cells expressing RET C634R in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639). 36166639
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Pralsetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and viability in transformed cells expressing RET C634R in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639). 36166639
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET C634R in culture (PMID: 37535881). 37535881
RET C634R Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical - Cell culture Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET C634R in culture (PMID: 37535881). 37535881
RET C634R malignant pheochromocytoma predicted - sensitive RET Inhibitor Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in stable disease lasting 9.4 months in a patient with metastatic pheochromocytoma harboring germline RET C634R and resulted in a partial response with treatment lasting 28.4 months in a second patient with metastatic pheochromocytoma harboring germline RET C634R (PMID: 38661071; NCT03157128). 38661071