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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 Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor ALW-II-41-27 Preclinical - Cell culture Actionable In a preclinical study, ALW-II-41-27 inhibited RET phosphorylation and downstream signaling and reduced proliferation of medullary thryoid carcinoma cells harboring RET M918T in culture (PMID: 26046350). 26046350
RET M918T Advanced Solid Tumor sensitive RET Inhibitor HG-6-63-01 Preclinical Actionable In a preclinical study, HG-6-63-01 inhibited RET phosphorylation and downstream signaling and reduced proliferation of transformed cells expressing RET M918T in culture (PMID: 26046350). 26046350
RET M918T Advanced Solid Tumor sensitive RET Inhibitor ALW-II-41-27 Preclinical - Cell culture Actionable In a preclinical study, ALW-II-41-27 inhibited RET phosphorylation and downstream signaling, reduced proliferation of transformed cells expressing RET M918T in culture (PMID: 26046350). 26046350
RET M918T thyroid gland medullary carcinoma sensitive AZD1480 Preclinical - Cell culture Actionable In a preclinical study, AZD1480 reduced phosphorylation of RET and downstream effectors, and inhibited growth and increased apoptosis of a medullary thyroid cancer cell line harboring RET M918T in culture (PMID: 23056499). 23056499
RET M918T thyroid gland carcinoma sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited RET signaling and decreased proliferation of thyroid carcinoma cells harboring a RET M918T mutation in culture (PMID: 23526464). 23526464
RET M918T lung small cell carcinoma sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited growth of small cell lung carcinoma lines expressing RET M918T (PMID: 25122427). 25122427
RET M918T Advanced Solid Tumor predicted - sensitive RET Inhibitor LOX-18228 Preclinical - Cell culture Actionable In a preclinical study, LOX-18228 treatment resulted in reduced viability in a cell line expressing RET M918T in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1464). detail...
RET M918T thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, and 4 of the 7 patients carried a RET M918T mutation (PMID: 26294908). 26294908
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Pralsetinib Phase Ib/II Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, and resulted in an overall response rate (ORR) of 65% (51/79, 5% complete response, 59% partial response) in patients with advanced or metastatic medullary thyroid cancer harboring RET mutations, 61% of the patients harbored RET M918T (Ann Oncol. Vol 31, Supplement 4, S1084, Sep 1, 2020; NCT03037385). detail...
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Pralsetinib Case Reports/Case Series Actionable In a Phase I trial, a patient with sporadic medullary thryoid cancer harboring RET M918T demonstrated a partial response, with maximal tumor reduction of 47% following treatment with Gavreto (pralsetinib) (PMID: 29657135; NCT03037385). 29657135
RET M918T 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 M918T in culture (PMID: 34373541). 34373541
RET M918T Advanced Solid Tumor sensitive RET Inhibitor Pz-1 Preclinical Actionable In a preclinical study, Pz-1 inhibited Ret phosphorylation in transformed cells expressing RET M918T (PMID: 26126987). 26126987
RET M918T Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited cell growth and Ret phosphorylation in transformed cells expressing RET M918T in culture (PMID: 33161056). 33161056
RET M918T Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing RET M918T were sensitive to treatment with Retevmo (selpercatinib) in culture, demonstrating decreased cell proliferation (PMID: 29912274). 29912274
RET M918T lung small cell carcinoma sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited growth of small cell lung carcinoma lines expressing RET M918T (PMID: 25122427). 25122427
RET M918T Advanced Solid Tumor sensitive RET Inhibitor XMD15-44 Preclinical Actionable In a preclinical study, XMD15-44 inhibited RET phosphorylation and downstream signaling and reduced proliferation of transformed cells expressing RET M918T in culture (PMID: 26046350). 26046350
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor HG-6-63-01 Preclinical Actionable In a preclinical study, HG-6-63-01 inhibited RET phosphorylation and downstream signaling and reduced proliferation of medullary thyroid carcinoma cells harboring RET M918T in culture (PMID: 26046350). 26046350
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Selpercatinib Case Reports/Case Series Actionable In a clinical case study, a pediatric patient with previously treated metastatic medullary thyroid cancer harboring germ line RET M918T mutation achieved stable disease and remained on treatment after 5.2 months with Retevmo (selpercatinib) therapy (PMID: 32923911). 32923911
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, thyroid medullary carcinoma cells harboring RET M918T were sensitive to treatment with Retevmo (selpercatinib) in culture, demonstrating decreased cell proliferation (PMID: 29912274). 29912274
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in rapid clinical improvement and complete resolution of the brain metastasis in a patient with metastatic medullary thyroid carcinoma harboring RET M918T whose disease progressed on prior Cometriq (cabozantinib) treatment, an official partial extracranial response was achieved at 1 year of treatment, until disease progression at 17 months (PMID: 33154983). 33154983
RET M918T Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation and transforming activity in cells expressing RET M918T in culture (PMID: 15184865). 15184865
RET M918T thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in partial response in 10% (1/10) and stable disease in 90% (9/10) of patients with medullary thyroid carcinoma harboring RET M918T (PMID: 20368568). 20368568
RET M918T Advanced Solid Tumor sensitive RET Inhibitor Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased proliferation of cells expressing RET M918T in culture (PMID: 17664273). 17664273
RET M918T colorectal cancer sensitive RET Inhibitor Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased growth of colorectal cancer cells harboring a RET M918T mutation in culture (PMID: 17664273). 17664273
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) increased overall survival to 25.4 months in medullary thyroid carcinoma patients with RET M918T (J Clin Oncol 33, 2015, suppl; abstr 6012). detail...
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (61 vs 17 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET M918T (PMID: 27525386). 27525386
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Cabozantinib Guideline Actionable Cometriq (cabozantinib) is included in guidelines for patients with advanced or metastatic medullary thyroid carcinoma harboring RET M918T (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Cabozantinib Case Reports/Case Series Actionable In a clinical case study, Cometriq (cabozantinib) treatment resulted in a partial response in a patient with medullary thyroid carcinoma with extensive CNS metastasis harboring MET M918T, although the patient experienced multiple adverse effects and her disease progressed after 8 months of treatment (PMID: 33154983). 33154983
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor XMD15-44 Preclinical Actionable In a preclinical study, XMD15-44 inhibited RET phosphorylation and downstream signaling and reduced proliferation of medullary thyroid carcinoma cells harboring RET M918T in culture (PMID: 26046350). 26046350
RET M918T Advanced Solid Tumor sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited phosphorylation of Ret in transformed human cells expressing RET M918T in culture (PMID: 23526464). 23526464
RET M918T thyroid gland medullary carcinoma sensitive RET Inhibitor Pz-1 Preclinical - Cell line xenograft Actionable In a preclinical study, Pz-1 treatment inhibited downstream signaling and growth of a medullary thyroid carcinoma cell line harboring RET M918T in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34373541). 34373541
RET M918T Advanced Solid Tumor predicted - sensitive RET Inhibitor APS03118 Preclinical - Biochemical Actionable In a preclinical study, APS03118 treatment inhibited Ret phosphorylation in transformed cells expressing RET M918T in culture (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries