Molecular Profile Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Profile Name RET G691S
Gene Variant Detail

RET G691S (gain of function)

Relevant Treatment Approaches RET Inhibitor

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET A883F 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 A883F in culture (PMID: 23526464). 23526464
RET A883F Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET A883F in culture (PMID: 15184865). 15184865
RET V804M RET S904C thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Compound germline RET V840M and S904C mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET C630X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET C630X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET C634R RET Y806F Advanced Solid Tumor predicted - sensitive RET Inhibitor Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET Y806F in culture demonstrated inhibition of Ret phosphorylation and activity in kinase assays when treated with Caprelsa (vandetanib) (PMID: 19029224). 19029224
RET C634W thyroid gland carcinoma sensitive RET Inhibitor Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased growth of thyroid carcinoma cells harboring a RET C634W mutation in culture (PMID: 17664273). 17664273
RET C634W thyroid gland medullary carcinoma sensitive RET Inhibitor Pralsetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and proliferation of a medullary thyroid cancer cell line harboring RET C634W in culture, and inhibited tumor growth in xenograft models (PMID: 29657135). detail... 29657135
RET C634W thyroid gland medullary carcinoma sensitive RET Inhibitor SYHA1815 Preclinical - Cell line xenograft Actionable In a preclinical study, SYHA1815 treatment inhibited RET signaling and proliferation of a medullary thyroid cancer cell line harboring RET C634W in culture, and induced tumor regression in a cell line xenograft model (PMID: 34518294). 34518294
RET C634W thyroid gland cancer sensitive RET Inhibitor Lenvatinib Preclinical Actionable In a preclinical study, Lenvima (lenvatinib) inhibited RET phosphorylation and signaling in thyroid cancer cells expressing RET C634W (PMID: 25295214). 25295214
RET C634W 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 C634W in culture (PMID: 26046350). 26046350
RET C634W thyroid gland carcinoma sensitive RET Inhibitor Cabozantinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cometriq (cabozantinib) inhibited phosphorylation of RET C634W and decreased tumor growth in xenograft models of a human thyroid carcinoma cell line harboring RET C634W mutation (PMID: 23705946). 23705946
RET C634W thyroid gland medullary carcinoma sensitive RET Inhibitor Selpercatinib Preclinical - Cell line xenograft Actionable In a preclinical study, thyroid medullary carcinoma cells harboring RET C634W were sensitive to treatment with Retevmo (selpercatinib), demonstrating decreased cell proliferation in culture and inhibition of tumor growth in cell line xenograft models (PMID: 29912274). 29912274
RET C634W thyroid gland carcinoma sensitive RET Inhibitor Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited RET signaling and decreased growth of thyroid carcinoma cells harboring a RET C634W mutation in culture and in cell line xenograft models (PMID: 23526464). 23526464
RET C634W thyroid gland cancer predicted - sensitive RET Inhibitor APS03118 Preclinical - Cell line xenograft Actionable In a preclinical study, APS03118 treatment inhibited proliferation of a thyroid cancer cell line harboring RET C634W in culture and inhibited tumor growth in a xenograft model (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
RET C634W thyroid gland cancer 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 thyroid cancer cell line harboring RET C634W in culture (PMID: 23056499). 23056499
RET C634W 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 C634W in culture (PMID: 26046350). 26046350
RET C634W thyroid gland medullary carcinoma sensitive RET Inhibitor Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and inhibited tumor growth in cell line xenograft models of medullary thyroid carcinoma harboring RET C634W (PMID: 16507829). 16507829
RET C634W thyroid gland cancer sensitive RET Inhibitor Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of thyroid cancer cells harboring RET C634W in culture (PMID: 21170960). 21170960
RET C634W thyroid gland medullary carcinoma sensitive RET Inhibitor RXDX-105 Preclinical - Cell culture Actionable In a preclinical study, RXDX-105 (CEP-32496) reduced phosphorylation of RET and downstream signaling and inhibited proliferation of a medullary thyroid cancer cell line harboring RET C634W in culture (PMID: 28011461). 28011461
RET C634W 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 thyroid carcinoma cells harboring RET C634W in culture (PMID: 26046350). 26046350
RET C634W 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 cell growth of a medullary thyroid carcinoma cell line harboring RET C634W in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34373541). 34373541
KDR pos RET C634W thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor Motesanib Diphosphate Preclinical - Cell line xenograft Actionable In a preclinical study, Motesanib (AMG 706) inhibited KDR (VEGFR2) phosphorylation, but had minimal activity against RET in a medullary thyroid carcinoma (MTC) cell line harboring RET C634W in culture, however, inhibited both RET and KDR (VEGFR2) phosphorylation and decreased tumor angiogenesis and growth in MTC cell line xenograft models with RET C634W (PMID: 21422803). 21422803
RET fusion differentiated thyroid gland carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for adult or pediatric patients 12 years or older with radioactive iodine-refractory, advanced or metastatic differentiated thyroid gland carcinoma harboring RET fusions (PMID: 31549998, PMID: 35491008; ESMO.org). 35491008 31549998 detail...
RET fusion pancreatic cancer predicted - sensitive RET Inhibitor Pralsetinib Case Reports/Case Series Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in a partial response in 2 of 2 patients with RET fusion positive pancreatic cancer, with a duration of response of 5.5 and 7.4 months, respectively (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion Advanced Solid Tumor predicted - sensitive RET Inhibitor Pralsetinib Phase Ib/II Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in an objective response rate of 60% (3/5) in patients with RET fusion positive advanced solid tumors other than thyroid cancer and non-small cell lung cancer (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion thyroid gland follicular carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for patients with follicular thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland papillary carcinoma sensitive RET Inhibitor Selpercatinib Phase I Actionable In a Phase I trial, Retevmo (selpercatinib) treatment resulted in an objective response rate of 83% (5/6) in RET fusion-positive papillary thyroid cancer patients (J Clin Oncol 36, 2018 (suppl; abstr 102); NCT03157128). detail...
RET fusion thyroid gland papillary carcinoma sensitive RET Inhibitor Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with papillary thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland cancer sensitive RET Inhibitor Pralsetinib FDA approved Actionable In a Phase I/II trial (ARROW) that supported FDA approval, Gavreto (pralsetinib) treatment was well-tolerated, and resulted in an overall response rate (ORR) of 89% (8/9) in patients with advanced or metastatic RET fusion-positive thyroid cancer, with a median duration of response of 14.5 months, and 67% of responding patients continuing treatment (PMID: 34118198; NCT03037385). 34118198 detail...
RET fusion lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was 25.7 mo in patients harboring RET fusions (n=4), although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
RET fusion extrahepatic bile duct carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) or subsequent-line therapy (category 2B) for patients with unresectable or metastatic extrahepatic cholangiocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion lung non-small cell carcinoma sensitive RET Inhibitor Pralsetinib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial (ARROW) that supported FDA approval, Gavreto (pralsetinib) treatment was well-tolerated, resulting in an objective response rate of 61% (53/87) and 70% (19/27) in previously treated and treatment-naive patients with RET fusion-positive non-small cell lung cancer, respectively (PMID: 34118197; NCT03037385). detail... 34118197 detail...
RET fusion thyroid gland cancer sensitive RET Inhibitor Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate of 79% (15/19), including one complete and 14 partial responses, with a median response duration of 18.4 months, and median progression-free survival of 20.1 months in adult and pediatric patients 12 years and older with RET fusion-positive thyroid cancer who were previously treated (PMID: 32846061; NCT03157128). detail... 32846061
RET fusion lung non-small cell carcinoma sensitive RET Inhibitor Vandetanib Phase II Actionable In a Phase II trial, Caprelsa (vandetanib) treatment resulted in a disease control rate of 88% (15/17), median progression-free survival (PFS) of 4.7 months, and partial response in 53% (9/17) of non-small cell lung adenocarcinoma patients harboring RET fusions (J Clin Oncol 34, 2016 (suppl; abstr 9012)). detail...
RET fusion lung non-small cell carcinoma sensitive RET Inhibitor Vandetanib Phase II Actionable In a Phase II trial, Caprelsa (vandetanib) treatment resulted in partial remission in 17% (3/18) and stable disease in 44% (8/18) of non-small cell lung adenocarcinoma patients harboring RET fusions (J Clin Oncol 34, 2016 (suppl; abstr 9013)). detail...
RET fusion Erdheim-Chester disease sensitive RET Inhibitor Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring RET fusions (NCCN.org). detail...
RET fusion colon cancer predicted - sensitive RET Inhibitor Pralsetinib Case Reports/Case Series Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in stable disease in 2 patients with RET fusion-positive colon cancer, with a duration of response of 7.3 and 9.3 months, respectively (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion thyroid gland Hurthle cell carcinoma sensitive RET Inhibitor Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with thyroid Hurthle cell carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland Hurthle cell carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for patients with thyroid Hurthle cell carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion gallbladder cancer sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) or subsequent-line therapy (category 2B) for patients with unresectable or metastatic gallbladder cancer harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland follicular carcinoma sensitive RET Inhibitor Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with follicular thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland anaplastic carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as systemic therapy for patients with anaplastic thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion intrahepatic cholangiocarcinoma sensitive RET Inhibitor Pralsetinib Case Reports/Case Series Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in a partial response in a patient with RET fusion-positive intrahepatic cholangiocarcinoma, with a duration of response of 7.5 months (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion intrahepatic cholangiocarcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) or subsequent-line therapy (category 2B) for patients with unresectable or metastatic intrahepatic cholangiocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland papillary carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as systemic therapy for patients with papillary thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland papillary carcinoma sensitive RET Inhibitor Pralsetinib Phase Ib/II Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in an objective response rate of 75% (9/12) and a median duration of response of 14.5 months in patients with RET fusion positive papillary thyroid cancer (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion thyroid gland medullary carcinoma sensitive RET Inhibitor Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with medullary thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland medullary carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as systemic therapy for patients with medullary thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion lung non-small cell carcinoma sensitive RET Inhibitor Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 64% (64/105) in patients with RET fusion-positive non-small cell lung cancer, with a median duration of response of 17.5 months, ORR was 85% (33/39) and 91% (10/11) in previously treated patients and patients with measurable CNS metastasis, respectively (PMID: 32846060; NCT03157128). detail... 32846060
RET fusion thyroid gland anaplastic carcinoma sensitive RET Inhibitor Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with anaplastic thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion differentiated thyroid gland carcinoma sensitive RET Inhibitor Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with advanced or metastatic differentiated thyroid gland carcinoma harboring RET fusions (PMID: 31549998, PMID: 35491008; ESMO.org). 35491008 31549998 detail...
RET L790X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET L790X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET C634R 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 50% (1/2) and stable disease in 50% (1/2) of patients with medullary thyroid carcinoma harboring RET C634R (PMID: 20368568). 20368568
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 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 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 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 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 Ponatinib Preclinical Actionable In a preclinical study, transformed human cell lines expressing RET C634R demonstrated sensitivity to Iclusig (ponatinib) (PMID: 23811235). 23811235
RET C634R RET V804G Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, transformed cell lines expressing Ret protein carrying both C634R and V804G mutations were more sensitive to Vandetanib induced inhibition of Ret activity than cells expressing Ret C634R alone in culture (PMID: 15184865). 15184865
RET C634R RET V804M Advanced Solid Tumor resistant RET Inhibitor Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET V804M were resistant to treatment with Caprelsa (vandetanib) in culture (PMID: 19029224). 19029224
RET C634R RET Y806C Advanced Solid Tumor resistant RET Inhibitor Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET Y806C were resistant to treatment with Caprelsa (vandetanib) in culture (PMID: 19029224). 19029224
RET C634R RET Y806E Advanced Solid Tumor resistant RET Inhibitor Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET Y806E were resistant to treatment with Caprelsa (vandetanib) in culture (PMID: 19029224). 19029224
RET rearrange lung adenocarcinoma predicted - sensitive RET Inhibitor Cabozantinib Phase II Actionable In a Phase II trial, treatment with Cometriq (cabozantinib) resulted in an overall response rate of 28% (7/25) in patients with RET-rearranged lung adenocarcinoma, with a median duration of response of 7.0 months (PMID: 27825636; NCT01639508). 27825636
RET rearrange lung non-small cell carcinoma no benefit RET Inhibitor Ponatinib Case Reports/Case Series Actionable In a retrospective analysis, multikinase inhibitor treatment demonstrated suboptimal clinical efficacy in RET-rearranged non-small cell lung cancer patients with measurable baseline brain metastasis, with a confirmed intracranial response rate of 18% (2/11); Iclusig (ponatinib) treatment resulted in no intracranial response in 4 patients with evaluable brain metastasis (PMID: 30017832). 30017832
RET rearrange lung non-small cell carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as a first-line therapy for non-small cell lung cancer patients with RET rearrangements (NCCN.org). detail...
RET rearrange lung non-small cell carcinoma sensitive RET Inhibitor Cabozantinib Guideline Actionable Cometriq (cabozantinib) is in guidelines for non-small cell lung cancer patients with RET rearrangements (NCCN.org). detail...
RET rearrange lung non-small cell carcinoma sensitive RET Inhibitor Cabozantinib Clinical Study Actionable In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 37% (7/19), with complete response in 5% (1/19) and partial response in 32% (6/19) of patients, and stable disease in 26% (5/19) of patients following Cometriq (cabozantinib) treatment (PMID: 28447912). 28447912
RET rearrange lung non-small cell carcinoma sensitive RET Inhibitor Selpercatinib Guideline Actionable Retevmo (selpercatinib) is in guidelines for non-small cell lung cancer patients with RET rearrangements (NCCN.org). detail...
RET rearrange lung non-small cell carcinoma sensitive RET Inhibitor Vandetanib Clinical Study Actionable In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/11, all partial responses) and stable disease in 27% (3/11) of patients following Caprelsa (vandetanib) treatment (PMID: 28447912). 28447912
RET rearrange lung non-small cell carcinoma sensitive RET Inhibitor Vandetanib Phase II Actionable In a Phase II trial, treatment with Caprelsa (vandetanib) resulted in an objective response rate of 18% (3/17, all partial responses) and disease control rate of 65% (stable disease in 47% (8/17) + partial response in 18% (3/17)) and median progression-free survival of 4.5 months in patients with RET-rearranged metastatic or recurrent non-small cell lung cancer (PMID: 27803005; NCT01823068). 27803005
RET rearrange lung non-small cell carcinoma predicted - sensitive RET Inhibitor RXDX-105 Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung cancer harboring a RET rearrangement demonstrated a sustained partial response following treatment with RXDX-105 (CEP-32496) on a Phase Ib clinical trial (PMID: 28011461; NCT01877811). 28011461
RET rearrange lung non-small cell carcinoma predicted - sensitive RET Inhibitor RXDX-105 Phase I Actionable In a Phase Ib trial, treatment with RXDX-105 (CEP-32496) resulted in an overall response rate of 19% (6/31) and stable disease in 39% (12/31) of patients with treatment-naive non-small cell lung cancer harboring a RET fusion (PMID: 30487236; NCT01877811) 30487236
RET rearrange lung adenocarcinoma no benefit RET Inhibitor Sunitinib Clinical Study - Cohort Actionable In a Phase II trial, Sutent (sunitinib) treatment demonstrated limited clinical efficacy, with no objective responses and stable disease in 71% (5/7) of lung adenocarcinoma patients harboring RET rearrangements (PMID: 32312893; NCT01829217). 32312893
RET rearrange thyroid gland papillary carcinoma sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) decreased proliferation of papillary thyroid carcinoma cells harboring the RET/PTC1 rearrangement in culture (PMID: 23526464). 23526464
RET rearrange Advanced Solid Tumor sensitive RET Inhibitor RXDX-105 Preclinical - Pdx Actionable In a preclinical study, CEP-32496 (RXDX-105) induced tumor regression in patient-derived xenograft models of several advanced solid tumor type with RET rearrangements (2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; Abstract A174). detail...
RET rearrange thyroid gland papillary carcinoma sensitive RET Inhibitor Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and activation of downstream signaling, and decreased growth of papillary thyroid carcinoma cells harboring the RET/PTC1 oncogene in culture (PMID: 17664273). 17664273
RET rearrange lung non-small cell carcinoma predicted - sensitive RET Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical study, Alecensa (alectinib) treatment resulted in objective radiographic response in 50% (2/4) and stable disease in 25% (1/4) of non-small cell lung carcinoma patients harboring RET rearrangement (PMID: 27544060). 27544060
RET rearrange lung non-small cell carcinoma predicted - sensitive RET Inhibitor Alectinib Case Reports/Case Series Actionable In a retrospective analysis, Alecensa (alectinib) treatment resulted an intracranial response in 1 of 2 patients with RET-rearranged non-small cell lung cancer (PMID: 30017832). 30017832
RET rearrange lung non-small cell carcinoma predicted - sensitive RET Inhibitor Sunitinib Clinical Study Actionable In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/9, all partial responses), and stable disease in 33% (3/9) of patients following Sutent (sunitinib) treatment (PMID: 28447912). 28447912
RET L629P RET D631_R635delinsG RET V637R thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor Pralsetinib Case Reports/Case Series Actionable In a Phase I trial, a patient with medullary thryoid cancer harboring RET D631_R635delinsG, L629P, and V637R demonstrated a partial response, with maximal tumor reduction of 47% at 10 months, following treatment with Gavreto (pralsetinib) (PMID: 29657135; NCT03037385). 29657135
RET R886W Advanced Solid Tumor sensitive RET Inhibitor Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing RET R886W were sensitive to treatment with Nexavar (sorafenib) in culture, demonstrating reduced cell proliferation (PMID: 21551259). 21551259
RET G810R Advanced Solid Tumor predicted - sensitive RET Inhibitor APS03118 Preclinical - Cell culture Actionable In a preclinical study, APS03118 inhibited the enzymatic activity of RET G810R in an in vitro assay and inhibited Ret phosphorylation and proliferation of cells expressing RET G810R in culture (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
RET G810R Advanced Solid Tumor predicted - sensitive RET Inhibitor TPX-0046 Preclinical - Cell culture Actionable In a preclinical study, TPX-0046 treatment led to inhibition of cell proliferation in a transformed cell line expressing RET G810R in culture (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 3616-3616). detail...
RET mutant cancer sensitive RET Inhibitor Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited wild-type RET and RET mutations to prevent cell proliferation in cell culture (PMID: 17664273). 17664273
RET mutant colorectal cancer sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) demonstrated efficacy in RET mutant positive colorectal cancer cell lines (PMID: 23811235). 23811235
RET mutant 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 (60 vs 20 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET mutations (PMID: 27525386). 27525386
RET mutant thyroid gland medullary carcinoma sensitive RET Inhibitor Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced or metastatic medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant thyroid gland medullary carcinoma sensitive RET Inhibitor Pralsetinib FDA approved Actionable In a Phase I/II trial (ARROW) that supported FDA approval, Gavreto (pralsetinib) treatment was well-tolerated and resulted in an overall response rate (ORR) of 60% (3/55) in patients with advanced or metastatic medullary thyroid cancer harboring RET mutations who received prior treatments, ORR was 60% (32/53) in patients with prior therapies and 71% (15/21) in treatment-naive patients (PMID: 34118198; NCT03037385). 34118198 detail...
RET mutant Advanced Solid Tumor sensitive RET Inhibitor Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of cancer cell lines harboring RET mutations in cultured and in cell line xenograft models (PMID: 23526464). 23526464
RET mutant thyroid gland medullary carcinoma sensitive RET Inhibitor Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55), with five complete and 33 partial responses, in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations who were previously treated, while patients who had not been previously treated demonstrated an ORR of 73% (64/88), with ten complete and 54 partial responses (PMID: 32846061; NCT03157128). detail... 32846061
RET mutant thyroid gland medullary carcinoma sensitive RET Inhibitor Selpercatinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant 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, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908). 26294908
RET mutant lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was 44.9 mo in a patient harboring RET mutation, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
RET mutant pheochromocytoma predicted - sensitive RET Inhibitor Sunitinib Case Reports/Case Series Actionable In a Phase II trial (SNIPP), a patient with pheochromocytoma harboring a germline RET mutation achieved a partial response to treatment with Sutent (sunitinib), and demonstrated a 64% reduction in tumor volume and remained on treatment for over 7 years (PMID: 31105270). 31105270
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 thyroid gland medullary carcinoma sensitive RET Inhibitor Selpercatinib Phase I 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 Pz-1 Preclinical Actionable In a preclinical study, Pz-1 inhibited Ret phosphorylation in transformed cells expressing RET V804M (PMID: 26126987). 26126987
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 RET Y806C Advanced Solid Tumor decreased response RET Inhibitor Selpercatinib Preclinical - Biochemical Actionable In a preclinical study, transformed human cells expressing RET V804M and Y806C in cis were less sensitive to Retevmo (selpercatinib) in culture (PMID: 35304457). 35304457
RET V804M RET Y806C thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Compound germline RET V840M and Y806C mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET V804M RET E805K thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Compound germline RET V840M and E805K mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET V804M RET M918T Advanced Solid Tumor predicted - 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 V804M and M918T in culture (PMID: 33161056). 33161056
RET V804M RET M918T thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor 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 M918T thyroid gland medullary carcinoma resistant RET Inhibitor 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 lung adenocarcinoma resistant RET Inhibitor 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 G810S RET L881V RET M918T thyroid gland medullary carcinoma predicted - resistant RET Inhibitor 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
RET V804M RET G810C RET M918T Advanced Solid Tumor resistant RET Inhibitor 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 RET Inhibitor 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
RET V804M RET Y806C RET M918T Advanced Solid Tumor predicted - resistant RET Inhibitor 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 G691S Advanced Solid Tumor predicted - sensitive Dovitinib Case Reports/Case Series Actionable In a Phase I clinical trial, two patients with germline RET G691S mutations demonstrated sensitivity to Dovitinib (TKI258) treatment (PMID: 25103625). 25103625
RET E768X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET E768X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET L790F 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 L790F in culture (PMID: 23526464). 23526464
RET L790F Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET L790F in culture (PMID: 15184865). 15184865
RET Y791X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET Y791X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET A883X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET A883X mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET D898V 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 D898V in culture (PMID: 23526464). 23526464
RET over exp breast cancer sensitive RET Inhibitor Y078-DM1 Preclinical - Cell line xenograft Actionable In a preclinical study, Y078-DM1 induced cytotoxicity in a human breast cancer cell line with high levels of RET expression in culture and inhibited tumor growth in xenograft models (PMID: 26240273). 26240273
RET over exp Advanced Solid Tumor predicted - sensitive RET Inhibitor Cabozantinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) treatment resulted in moderate tumor volume reduction in a cell line xenograft model of transformed cells overexpressing RET (PMID: 30446652). 30446652
RET C620X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET C620X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET wild-type 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 wild-type RET (PMID: 25122427). 25122427
RET wild-type 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 wild-type RET (PMID: 25122427). 25122427
RET act mut lung non-small cell carcinoma sensitive RET Inhibitor Ponatinib Preclinical - Cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited RET phosphorylation and reduced viability of non-small cell lung cancer cells with RET activating mutations (Cancer Res April 15, 2013 73; 2084). detail...
RET C634F thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in stable disease in one patient with medullary thyroid carcinoma harboring RET C634F (PMID: 20368568). 20368568
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 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 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 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 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 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, Retevmo (selpercatinib) inhibited Erk phosphorylation and growth of transformed cells expressing RET M918T in culture (PMID: 32284345). 32284345
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 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 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 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 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 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 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 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 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 Advanced Solid Tumor predicted - sensitive RET Inhibitor APS03118 Preclinical - Biochemical Actionable In a preclinical study, APS03118 treatment inhibited Ret phosphorylation in cells expressing RET M918T in culture (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
RET M918T Advanced Solid Tumor sensitive RET Inhibitor Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Erk phosphorylation and growth of transformed cells expressing RET M918T in culture (PMID: 32284345). 32284345
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 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 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 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 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 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 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 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 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 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 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
ATM L804fs ATM S978fs RET M918T thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor 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 C609X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET C609X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET G810S Advanced Solid Tumor predicted - sensitive RET Inhibitor TPX-0046 Preclinical - Cell culture Actionable In a preclinical study, TPX-0046 treatment led to inhibition of cell proliferation in a transformed cell line expressing RET G810S in culture (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 3616-3616). detail...
RET G810S Advanced Solid Tumor predicted - sensitive RET Inhibitor APS03118 Preclinical - Cell culture Actionable In a preclinical study, APS03118 inhibited the enzymatic activity of RET G810S in an in vitro assay and inhibited proliferation of cells expressing RET G810S in culture (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
RET C611X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET C611X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET S891A 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 S891A in culture (PMID: 23526464). 23526464
RET S891A Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET S891A in culture (PMID: 15184865). 15184865
RET S891A Advanced Solid Tumor sensitive RET Inhibitor Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation in cells expressing RET S891A in culture (PMID: 17664273). 17664273
RET V804L 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 V804L or RET V804M who had been treated previously (PMID: 32846061; NCT03157128). 32846061
RET V804L Advanced Solid Tumor predicted - sensitive RET Inhibitor APS03118 Preclinical - Biochemical Actionable In a preclinical study, APS03118 inhibited the enzymatic activity of RET V804L in an in vitro assay (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
RET V804L 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 V804L (PMID: 26126987). 26126987
RET V804L Advanced Solid Tumor sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, transformed human cell lines expressing RET V804L demonstrated sensitivity to Iclusig (ponatinib) (PMID: 23811235). 23811235
RET V804L Advanced Solid Tumor resistant RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, transformed cells expressing RET V804L demonstrated resistance to growth inhibition by Caprelsa (vandetanib) in culture (PMID: 15184865). 15184865
RET C634X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET C634X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET C634X 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, 28% of the patients harbored RET C634X (Ann Oncol. Vol 31, Supplement 4, S1084, Sep 1, 2020; NCT03037385). detail...
RET T930K Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited growth of transformed cells expressing RET T930K in culture (PMID: 32284345). 32284345
RET T930K Advanced Solid Tumor sensitive RET Inhibitor Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited growth of transformed cells expressing RET T930K in culture (PMID: 32284345). 32284345
RET C634Y 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 C634Y in culture (PMID: 26046350). 26046350
RET C634Y 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 C634Y in culture (PMID: 26046350). 26046350
RET C634Y Advanced Solid Tumor sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of transformed cells harboring RET C634Y in culture (PMID: 23526464). 23526464
RET C634Y thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in stable disease in one patient with medullary thyroid carcinoma harboring RET C634Y (PMID: 20368568). 20368568
RET C634Y 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 C634Y in culture (PMID: 26046350). 26046350
RET C620R thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease of 116 weeks in a MEN2A patient with medullary thyroid cancer carrying a RET C620R mutation (PMID: 26294908). 26294908
RET D898_E901del Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Erk phosphorylation and growth of transformed cells expressing RET D898_E901del in culture (PMID: 32284345). 32284345
RET D898_E901del Advanced Solid Tumor sensitive RET Inhibitor Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Erk phosphorylation and growth of transformed cells expressing RET D898_E901del in culture (PMID: 32284345). 32284345
RET D378_G385delinsE thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor Selpercatinib Case Reports/Case Series Actionable In a clinical case study, a pediatric patient with heavily pretreated medullary thyroid cancer harboring RET D378_G385delinsE achieved a partial response after 8 weeks of Retevmo (selpercatinib) treatment, with an 86% reduction in tumor size after 40 weeks, and remained progression-free after 27 months (PMID: 32923911; NCT03157128). 32923911
RET - SEPTIN9 malignant pheochromocytoma predicted - sensitive RET Inhibitor Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a partial response with 46% reduction in lesions, which was ongoing at 23 weeks, in a patient with malignant pheochromocytoma harboring a RET-SEPTIN9 fusion (PMID: 34994633). 34994633
RET C618X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET C618X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET V804X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET V804X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET V804X 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, 4% of the patients harbored RET V804X (Ann Oncol. Vol 31, Supplement 4, S1084, Sep 1, 2020; NCT03037385). detail...
RET C618R thyroid gland medullary carcinoma predicted - sensitive RET Inhibitor Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in stable disease in one patient with medullary thyroid carcinoma harboring RET C618R (PMID: 20368568). 20368568
RET E884K 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 E884K in culture (PMID: 23526464). 23526464
RET V804E Advanced Solid Tumor predicted - sensitive RET Inhibitor APS03118 Preclinical - Biochemical Actionable In a preclinical study, APS03118 inhibited the enzymatic activity of RET V804E in an in vitro assay (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
RET G810C Advanced Solid Tumor predicted - sensitive RET Inhibitor TPX-0046 Preclinical - Cell culture Actionable In a preclinical study, TPX-0046 treatment led to inhibition of cell proliferation in a transformed cell line expressing RET G810C in culture (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 3616-3616). detail...
RET G810C Advanced Solid Tumor predicted - sensitive RET Inhibitor APS03118 Preclinical - Biochemical Actionable In a preclinical study, APS03118 inhibited the enzymatic activity of RET G810C in an in vitro assay (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...
RET S891X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET S891X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org). detail...
RET Y806C 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 Y806C in culture (PMID: 23526464). 23526464
RET Y791F 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 Y971F in culture (PMID: 23526464). 23526464
RET Y791F Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET Y791F in culture (PMID: 15184865). 15184865
RET E768D Advanced Solid Tumor sensitive RET Inhibitor Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET E768D in culture (PMID: 15184865). 15184865
RET E768D 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 E768D in culture (PMID: 23526464). 23526464
RET T930P Advanced Solid Tumor sensitive RET Inhibitor Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited growth of transformed cells expressing RET T930P in culture (PMID: 32284345). 32284345
RET T930P Advanced Solid Tumor sensitive RET Inhibitor Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited growth of transformed cells expressing RET T930P in culture (PMID: 32284345). 32284345
RET positive breast cancer sensitive RET Inhibitor Y078-DM4 Preclinical - Cell line xenograft Actionable In a preclinical study, Y078-DM4 induced cytotoxicity in RET-expressing human breast cancer cell lines in culture and inhibited tumor growth in xenograft models (PMID: 26240273). 26240273
RET positive thyroid gland medullary carcinoma sensitive RET Inhibitor Y078-DM4 Preclinical Actionable In a preclinical study, Y078-DM4 induced cytotoxicity in a RET-expressing medullary thyroid cell line in culture (PMID: 26240273). 26240273
RET M918X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET M918X mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). detail...
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries