Molecular Profile Detail

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Profile Name	RET V804M
Gene Variant Detail	RET V804M (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 V804M	Advanced Solid Tumor	sensitive	RET Inhibitor	Ponatinib	Preclinical	Actionable	In a preclinical study, transformed human cell lines expressing RET V804M demonstrated sensitivity to Iclusig (ponatinib) (PMID: 23811235).	23811235
RET V804M	Advanced Solid Tumor	sensitive	RET Inhibitor	Sorafenib	Preclinical	Actionable	In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased growth of transformed cells expressing RET V804M in culture (PMID: 16507829).	16507829
RET V804M	Advanced Solid Tumor	resistant	RET Inhibitor	Vandetanib	Preclinical	Actionable	In a preclinical study, transformed cells expressing RET V804M demonstrated resistance to growth inhibition by Caprelsa (vandetanib) in culture (PMID: 15184865).	15184865
RET V804M	Advanced Solid Tumor	predicted - sensitive	RET Inhibitor	Pz-1	Preclinical	Actionable	In a preclinical study, Pz-1 inhibited Ret phosphorylation in transformed cells expressing RET V804M (PMID: 26126987).	26126987
RET V804M	thyroid gland medullary carcinoma	sensitive	RET Inhibitor	Selpercatinib	Case Reports/Case Series	Actionable	In a Phase I trial, Retevmo (selpercatinib) treatment resulted in partial response in a thyroid medullary cancer patient harboring RET V804M (J Clin Oncol 36, 2018 (suppl; abstr 102); NCT03157128).	detail...
RET V804M	thyroid gland medullary carcinoma	sensitive	RET Inhibitor	Selpercatinib	Case Reports/Case Series	Actionable	In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in an objective response in three patients (3/5) and stable disease in two patients (2/5) with medullary thyroid cancer harboring RET V804M or RET V804L who were previously treated (PMID: 32846061; NCT03157128).	detail... 32846061
RET V804M	Advanced Solid Tumor	predicted - sensitive	RET Inhibitor	APS03118	Preclinical - Biochemical	Actionable	In a preclinical study, APS03118 inhibited the enzymatic activity of RET V804M in an in vitro assay, inhibited Ret phosphorylation in cells expressing RET V804M in culture, and inhibited tumor growth in cell line xenograft models expressing RET V804M (J Clin Oncol 40, no. 16_suppl (June 1, 2022)).	detail...
RET V804M	Advanced Solid Tumor	predicted - sensitive	RET Inhibitor	TY-1091	Preclinical - Biochemical	Actionable	In a preclinical study, TY-1091 inhibited activity in a cell line expressing RET V804M in culture (Cancer Res (2023) 83 (7_Supplement): 3419).	detail...
RET V804M	Advanced Solid Tumor	predicted - sensitive	RET Inhibitor	FHND5071	Preclinical - Cell culture	Actionable	In a preclinical study, FHND5071 inhibited Ret phosphorylation and proliferation in cells expressing RET V804M in culture (Cancer Res (2023) 83 (8_Supplement): LB330).	detail...