Molecular Profile Detail

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Profile Name RET M918T
Gene Variant Detail

RET M918T (gain of function)

Relevant Treatment Approaches RET Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET V804M RET Y806C RET M918T Advanced Solid Tumor predicted - resistant Selpercatinib Preclinical - Biochemical Actionable In a preclinical study, transformed human cells expressing RET M918T, V804M, and Y806C in cis were resistant to Retevmo (selpercatinib) in culture (PMID: 35304457). 35304457
RET V804M RET G810S RET L881V RET M918T thyroid gland medullary carcinoma predicted - resistant Selpercatinib Case Reports/Case Series Actionable In a clinical case study, a patient with hereditary medullary thyroid carcinoma harboring germline RET M918T demonstrated disease progression following an initial response to Retevmo (selpercatinib), and ctDNA sequencing revealed a decrease in RET L881V, but an increase in RET V804M and RET G810S (PMID: 31988000). 31988000
ATM L804fs ATM S978fs RET M918T thyroid gland medullary carcinoma predicted - sensitive Everolimus + Vandetanib Case Reports/Case Series Actionable In a clinical case study, addition of Afinitor (everolimus) to Caprelsa (vandetanib) treatment resulted in significant tumor reduction in a medullary thyroid carcinoma patient harboring ATM L804fs*4, ATM S978fs*12, and RET M918T, that achieved prolonged stable disease on Caprelsa (vandetanib) treatment alone (PMID: 27683183). 27683183
RET V804M RET M918T thyroid gland medullary carcinoma resistant Everolimus + Vandetanib Case Reports/Case Series Actionable In a clinical case study, a patient with thyroid medullary carcinoma harboring RET M918T progressed on multiple therapies, including Nexavar (sorafenib), Caprelsa (vandetanib), Cometriq (cabozantinib), MGCD-516 (sitravatinib), and RXDX-105 (CEP-32496), and upon progression with the combination therapy, Caprelsa (vandetanib) and Afinitor (everolimus), cell-free DNA testing revealed RET M918T and acquisition of a secondary drug resistant mutation, RET V804M (PMID: 29912274; NCT03157128). 29912274
RET V804M RET M918T Advanced Solid Tumor predicted - sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited cell growth and Ret phosphorylation in transformed cells expressing RET V804M and M918T in culture (PMID: 33161056). 33161056
RET V804M RET M918T lung adenocarcinoma resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma initially treated with chemotherapy and immunotherapy was found to harbor KIF5B-RET, and was then treated with Alecensa (alectinib), which resulted in an intracranial response, but eventually led to further progression (PMID: 29912274; NCT03157128). 29912274
RET V804M RET M918T thyroid gland medullary carcinoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, a patient with thyroid medullary cancer harboring RET M918T and RET V804M demonstrated an initial response to Retevmo (selpercatinib), which included a decrease in allelic fraction of RET M918T and RET V804M over 8 weeks and a radiographic response of nearly 54% post 6.9 months of treatment (PMID: 29912274; NCT03157128). 29912274
RET V804M RET G810C RET M918T Advanced Solid Tumor resistant Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing RET V804M, G810C, and M918T were resistant to Retevmo (selpercatinib) treatment in culture (PMID: 33161056). 33161056
RET V804M RET G810S RET M918T Advanced Solid Tumor resistant Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing RET V804M, G810S, and M918T were resistant to Retevmo (selpercatinib) treatment in culture (PMID: 33161056). 33161056
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries