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Gene Symbol RET
Synonyms CDHF12 | CDHR16 | HSCR1 | MEN2A | MEN2B | MTC1 | PTC | RET-ELE1
Gene Description RET, ret proto-oncogene, is a receptor tyrosine kinase that activates MAPK and PI3K/AKT pathways and regulates cell growth and differentiation (PMID: 24561444, PMID: 29134959, PMID: 32094155). RET germline mutations result in MEN2 syndromes and familial medullary thyroid carcinoma (PMID: 20930041, PMID: 24561444) and somatic RET activating mutations, fusions, and Ret amplification and/or overexpression has been associated with a variety of cancers including lung (PMID: 30257958) and colorectal (PMID: 30210625, PMID: 30038711).
ACMG Incidental List v3.0:
Yes, Multiple endocrine neoplasia type 2B (PMID: 34012068)
Yes, Multiple endocrine neoplasia type 2A (PMID: 34012068)
Yes, Familial medullary thyroid cancer (PMID: 34012068)
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
5979 10 10q11.21 NM_020975 Oncogene (PMID: 30606230)

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET wild-type lung small cell carcinoma sensitive 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 wild-type lung small cell carcinoma sensitive 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 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 Y791F Advanced Solid Tumor sensitive Ponatinib Preclinical - Biochemical Actionable In a preclinical study, Iclusig (ponatinib) inhibited phosphorylation of Ret in transformed human cells expressing RET Y791F in culture (PMID: 23526464). 23526464
RET Y791F Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET Y791F in culture (PMID: 15184865). 15184865
RET C634R Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed human cell lines expressing RET C634R demonstrated sensitivity to Iclusig (ponatinib) (PMID: 23811235). 23811235
RET C634R medullary thyroid carcinoma predicted - sensitive 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 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 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 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 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 Advanced Solid Tumor sensitive 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 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 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 malignant pheochromocytoma predicted - sensitive 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
RET C634R Advanced Solid Tumor sensitive 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 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 RET V804G Advanced Solid Tumor sensitive 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 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 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 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 C634R RET Y806F Advanced Solid Tumor predicted - sensitive 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 mutant medullary thyroid carcinoma sensitive Everolimus Phase II Actionable In a Phase II 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; NCT01118065). 26294908
RET mutant colorectal cancer sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) demonstrated efficacy in RET mutant positive colorectal cancer cell lines (PMID: 23811235). 23811235
RET mutant Advanced Solid Tumor sensitive 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 cancer sensitive 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 pheochromocytoma predicted - sensitive 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 mutant medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines (category 2B) for patients with medullary thyroid carcinoma harboring RET mutations (NCCN.org). detail...
RET mutant medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 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
RET mutant medullary thyroid carcinoma sensitive Selpercatinib FDA approved - Has Companion Diagnostic 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... detail... 32846061
RET mutant medullary thyroid carcinoma sensitive Selpercatinib FDA approved - Has Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-121) that supported FDA approval, Retevmo (selpercatinib) treatment was safe in pediatric patients of 2 years or older with solid tumors (8 medullary thyroid cancer, 2 papillary thyroid cancer, 1 osteosarcoma) harboring RET fusion (n=2) or mutations (n=9), and resulted in unconfirmed partial responses in 4 patients, stable disease in 6 patients (two lasting >/=16 weeks) (JCO 39, 10009-10009(2021); NCT03899792). detail... detail... detail...
RET mutant medullary thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) 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 medullary thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with medullary thyroid carcinoma harboring RET mutations (NCCN.org). detail...
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 lung non-small cell carcinoma predicted - sensitive EP0031 Phase Ib/II Actionable In a Phase I/II trial (KL400-I/II-01), EP0031 treatment was well tolerated in non-small cell lung cancer (NSCLC) patients harboring RET mutations, and resulted in an objective response rate (ORR) of 63% (20/32, 1 complete response (CR)) and disease control rate (DCR) of 91% in pretreated patients, and an ORR of 76% (19/25, 1 CR) and DCR of 92% with median duration of response not reached in treatment-naive patients, and an overall CNS DCR of 100% (J Clin Oncol 41, 2023 (suppl 16; abstr 3007); NCT05265091). detail...
RET mutant Advanced Solid Tumor predicted - sensitive EP0031 Phase Ib/II Actionable In a Phase I/II trial (KL400-I/II-01), EP0031 treatment was well tolerated and demonstrated preliminary activity in patients with advanced solid tumors harboring mutations in RET, resulting in an objective response rate of 64%, with responses being observed in patients with non-small cell lung cancer, medullary thyroid cancer and pancreatic cancer (J Clin Oncol 41, 2023 (suppl 16; abstr 3007); NCT05265091). detail...
RET rearrange lung non-small cell carcinoma predicted - sensitive 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 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 no benefit 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 papillary thyroid carcinoma sensitive 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 papillary thyroid carcinoma sensitive 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 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 rearrange lung adenocarcinoma no benefit 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 lung non-small cell carcinoma sensitive 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 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 sensitive Cabozantinib Guideline Actionable Cometriq (cabozantinib) is in guidelines as a first-line and subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org). detail...
RET rearrange lung non-small cell carcinoma sensitive 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 adenocarcinoma predicted - sensitive 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 predicted - sensitive 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 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 Advanced Solid Tumor sensitive 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 lung non-small cell carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as a first-line and subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org). detail...
RET rearrange lung non-small cell carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is in guidelines as a first-line and subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org). detail...
RET amp glioblastoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a partial response in a patient with glioblastoma harboring RET amplification along with MDM2 and CDK4 amplification and an ATM splice mutation, who stayed on treatment for 8 months until disease progression (PMID: 36075388). 36075388
RET amp lung non-small cell carcinoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a complete response in the axillary lymph node and a partial response in the brain metastases in a patient with RET-amplified (CN=28) non-small cell lung cancer (PMID: 37972337). 37972337
RET act mut lung non-small cell carcinoma sensitive 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 V804M Advanced Solid Tumor sensitive 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 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 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 Pz-1 Preclinical Actionable In a preclinical study, Pz-1 inhibited Ret phosphorylation in transformed cells expressing RET V804M (PMID: 26126987). 26126987
RET V804M medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 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 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 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...
RET V804M RET S904C medullary thyroid carcinoma not applicable N/A Guideline Risk Factor Compound germline RET V804M 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 V804M RET Y806C medullary thyroid carcinoma not applicable N/A Guideline Risk Factor Compound germline RET V804M 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 Y806C Advanced Solid Tumor decreased response 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 E805K medullary thyroid carcinoma not applicable N/A Guideline Risk Factor Compound germline RET V804M 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 medullary thyroid 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 medullary thyroid 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 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 G810S RET L881V RET M918T medullary thyroid 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
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
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 Advanced Solid Tumor predicted - sensitive TY-1091 Preclinical - Biochemical Actionable In a preclinical study, TY-1091 inhibited activity in a cell line expressing RET G810S and V804M in culture (Cancer Res (2023) 83 (7_Supplement): 3419). detail...
RET V804L Advanced Solid Tumor sensitive 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 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 V804L Advanced Solid Tumor predicted - sensitive Pz-1 Preclinical Actionable In a preclinical study, Pz-1 inhibited Ret phosphorylation in transformed cells expressing RET V804L (PMID: 26126987). 26126987
RET V804L medullary thyroid carcinoma sensitive 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 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 TY-1091 Preclinical - Biochemical Actionable In a preclinical study, TY-1091 inhibited activity in a cell line expressing RET V804L in culture (Cancer Res (2023) 83 (7_Supplement): 3419). detail...
RET positive breast cancer sensitive 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 medullary thyroid carcinoma sensitive 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 fusion lung non-small cell carcinoma sensitive 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 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 colon cancer predicted - sensitive 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 cancer sensitive 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 pancreatic cancer predicted - sensitive 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 gallbladder cancer sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) and subsequent-line therapy (category 2B) for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including gallbladder cancer (NCCN.org). detail...
RET fusion lung non-small cell carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as a first-line therapy for patients with metastatic non-small cell lung cancer harboring RET fusions (PMID: 36872130; ESMO.org). detail... 36872130
RET fusion lung non-small cell carcinoma sensitive 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 lung non-small cell carcinoma sensitive Pralsetinib Clinical Study Actionable In a retrospective study, Gavreto (pralsetinib) treatment resulted in an objective response rate (ORR) of 61% (39/59, 2 complete responses (CR), 37 partial responses (PR)) and a disease control rate (DCR) of 79.7% in non-small cell lung cancer patients harboring RET fusions, and an intracranial ORR of 66.7% (4/6, 3 CR and 1 PR), an intracranial DCR of 100% in patients with measurable brain metastases (PMID: 36379124). 36379124
RET fusion lung non-small cell carcinoma sensitive Pralsetinib Clinical Study Actionable In a retrospective study, Gavreto (pralsetinib) treatment resulted in an overall response rate of 55.6%, a disease control rate of 72.2%, a median progression-free survival of 10.7 months, and overall survival of 21.2 months in patients with metastatic non-small cell lung cancer harboring a RET fusion (n=36) including KIF5B-RET (n=13) and CCDC6-RET (n=2) (PMID: 39241296). 39241296
RET fusion follicular thyroid carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for patients with follicular thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion papillary thyroid carcinoma sensitive 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 papillary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 extrahepatic bile duct carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) and subsequent-line therapy (category 2B) for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including extrahepatic cholangiocarcinoma (NCCN.org). detail...
RET fusion intrahepatic cholangiocarcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) and subsequent-line therapy (category 2B) for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including intrahepatic cholangiocarcinoma (NCCN.org). detail...
RET fusion intrahepatic cholangiocarcinoma sensitive 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 oncocytic carcinoma of the thyroid sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for patients with thyroid Hurthle cell carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion anaplastic thyroid carcinoma sensitive 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 differentiated high-grade thyroid carcinoma sensitive 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 Advanced Solid Tumor predicted - sensitive Pralsetinib Phase Ib/II Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well tolerated in patients with advanced solid tumors harboring RET fusions, and led to an overall response rate of 57% (13/23, 3 complete and 10 partial responses), a clinical benefit rate of 70% (16/23), a disease control rate of 83% (19/23), a median duration of response of 11.7 months, a median progression-free survival of 7.4 months, and a median overall survival of 13.6 months (PMID: 35962206; NCT03037385). 35962206
RET fusion neuroendocrine tumor sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring RET fusions who have progressed on or following prior treatment (NCCN.org). detail...
RET fusion colon cancer sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 43.9% (18/41, 2 complete responses, 16 partial responses) with a median duration of response (mDOR) of 24.5 months in patients with RET fusion-positive advanced or metastatic solid tumors, and ORR and mDOR in patients with colon cancer were 20.0% (2/10) and 9.4 months, respectively (PMID: 36108661; NCT03157128). 36108661
RET fusion colon cancer sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with metastatic colon cancer harboring RET fusions (NCCN.org). detail...
RET fusion hepatocellular carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hepatocellular carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion sarcoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as first-line therapy for patients with advanced or metastatic soft tissue sarcoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid cancer sensitive Selpercatinib FDA approved - On Companion Diagnostic 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... detail... 32846061
RET fusion thyroid cancer sensitive Selpercatinib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-121) that supported FDA approval, Retevmo (selpercatinib) treatment was safe in pediatric patients of 2 years or older with solid tumors (8 medullary thyroid cancer, 2 papillary thyroid cancer, 1 osteosarcoma) harboring RET fusion (n=2) or mutations (n=9), and resulted in unconfirmed partial responses in 4 patients, stable disease in 6 patients (two lasting >/=16 weeks) (JCO 39, 10009-10009(2021); NCT03899792). detail... detail... detail...
RET fusion pancreatic cancer predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 43.9% (18/41, 2 complete responses, 16 partial responses) with a median duration of response (mDOR) of 24.5 months in patients with RET fusion-positive advanced or metastatic solid tumors, and ORR and mDOR in patients with pancreatic cancer were 54.5% (6/11) and not reached, respectively (PMID: 36108661; NCT03157128). 36108661
RET fusion rectum cancer sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with metastatic rectum cancer harboring RET fusion (NCCN.org). detail...
RET fusion ovary epithelial cancer sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring a RET fusion (NCCN.org). detail...
RET fusion gallbladder cancer sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as primary (category 2B) and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including gallbladder cancer (NCCN.org). detail...
RET fusion ampulla of Vater adenocarcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion esophagus squamous cell carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion lung non-small cell carcinoma sensitive Selpercatinib FDA approved - On Companion Diagnostic 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 detail...
RET fusion lung non-small cell carcinoma sensitive Selpercatinib Phase III Actionable In a Phase III trial (LIBRETTO-431), first-line Retevmo (selpercatinib) treatment resulted in superior median progression-free survival (PFS) compared to platinum-based chemotherapy with (24.8 vs 11.2 mo, HR=0.46, p<0.001) or without ((24.8 vs 11.2 mo, HR=0.48, p<0.001) Keytruda (pembrolizumab) in advanced non-small cell lung cancer patients harboring a RET fusion, and improved intracranial (IC) response rate (82.4% vs 58.3%) and median IC PFS (16.1 vs 10.4 mo) (PMID: 38807655; NCT04194944). 38807655
RET fusion lung non-small cell carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as a first-line therapy for patients with metastatic non-small cell lung cancer harboring RET fusions (PMID: 36872130; ESMO.org). 36872130 detail...
RET fusion follicular thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with follicular thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion papillary thyroid carcinoma sensitive 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 papillary thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with papillary thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion medullary thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with medullary thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion pancreatic adenocarcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as first-line or subsequent therapy for patients with locally advanced, metastatic, or recurrent pancreatic adenocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion Erdheim-Chester disease sensitive 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 cervical cancer sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with cervical cancer harboring RET fusions (NCCN.org). detail...
RET fusion extrahepatic bile duct carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as primary (category 2B) and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including extrahepatic cholangiocarcinoma (NCCN.org). detail...
RET fusion small intestine adenocarcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with metastatic small bowel adenocarcinoma with RET fusion (NCCN.org). detail...
RET fusion esophagus adenocarcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic esophageal adenocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion intrahepatic cholangiocarcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as primary (category 2B) and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including intrahepatic cholangiocarcinoma (NCCN.org). detail...
RET fusion gastroesophageal junction adenocarcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion cholangiocarcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as primary (category 2B) or subsequent-line therapy (category 2A) for patients with unresectable or metastatic cholangiocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion oncocytic carcinoma of the thyroid sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with thyroid Hurthle cell carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion salivary gland cancer sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with recurrent, unresectable, or metastatic salivary gland tumors harboring RET fusions (NCCN.org). detail...
RET fusion stomach cancer sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring RET fusion (NCCN.org). (NCCN.org). detail...
RET fusion vaginal carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an RET fusion (NCCN.org). detail...
RET fusion anaplastic thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with anaplastic thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET fusion differentiated high-grade thyroid carcinoma sensitive 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 fusion Advanced Solid Tumor sensitive Selpercatinib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate of 44% (18/41, 2 complete responses, 16 partial responses), a clinical benefit rate of 63% (26/41), a median duration of response of 24.5 months, and a median progression-free survival of 13.2 months in patients with RET fusion-positive advanced solid tumors (PMID: 36108661; NCT03157128). 36108661 detail...
RET fusion Advanced Solid Tumor sensitive Selpercatinib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-121) that supported FDA approval, Retevmo (selpercatinib) treatment was safe in pediatric patients of 2 years or older with solid tumors harboring RET fusion (n=2) or mutations (n=9), and resulted in unconfirmed partial responses in 4 patients, stable disease in 6 patients (two lasting >/=16 weeks) (JCO 39, 10009-10009(2021); NCT03899792). detail... detail... detail...
RET fusion Adenocarcinoma of Unknown Primary sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring RET fusions (NCCN.org). detail...
RET fusion Squamous Cell Carcinoma of Unknown Primary sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring RET fusions (NCCN.org). 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 lung non-small cell carcinoma predicted - sensitive HS-10365 Phase I Actionable In a Phase I trial, HS-10365 treatment demonstrated safety and resulted in a response rate of 70% (21/30) and a disease control rate of 96.7% (29/30) in patients with non-small cell lung cancer harboring RET fusions (Cancer Res (2023) 83 (8_Supplement): CT201; NCT05207787). detail...
RET fusion lung non-small cell carcinoma sensitive SY-5007 Phase I Actionable In a Phase I trial, SY-5007 therapy was tolerable and led to an objective response rate (ORR) of 57.8% (67/116, 67 partial responses), disease control rate (DCR) of 95.7% (111/116), and median progression-free survival of 21.1 mo in advanced solid tumor patients with RET fusions or alterations, and an ORR of 64.1% (41/64) and DCR of 96.9% (62/64) at the phase II dose in non-small cell lung cancer patients with KIF5B (n=51), CCDC6 (n=12), NCOA4 (n=1), or other RET fusions (n=4) (PMID: 39489747; NCT05278364). 39489747
RET M918T medullary thyroid 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 medullary thyroid carcinoma predicted - sensitive Everolimus Case Reports/Case Series 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 harbored a RET M918T mutation (PMID: 26294908; NCT01118065). 26294908
RET M918T thyroid gland carcinoma sensitive 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 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 sensitive 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 medullary thyroid carcinoma predicted - sensitive Sorafenib Case Reports/Case Series 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; NCT00390325). 20368568
RET M918T colorectal cancer sensitive 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 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 lung small cell carcinoma sensitive 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 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 RET M918T, although the patient experienced multiple adverse effects and her disease progressed after 8 months of treatment (PMID: 33154983). 33154983
RET M918T medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 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 medullary thyroid carcinoma sensitive 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 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 medullary thyroid carcinoma sensitive 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 Advanced Solid Tumor sensitive 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 medullary thyroid carcinoma sensitive 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 sensitive 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 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 Advanced Solid Tumor sensitive 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 Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET M918T in culture (PMID: 36166639). 36166639
RET M918T thyroid gland carcinoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a partial response after 9 weeks of treatment, with a decrease in the size of the cervical and mediastinal lymph nodes, in a patient with metastatic recurrent mixed medullary and follicular cell-derived thyroid carcinoma harboring RET M918T, and response was maintained at 33 weeks post-treatment initiation (PMID: 38647958). 38647958
RET M918T medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a partial response in a pediatric patient with medullary thyroid carcinoma harboring RET M918T (PMID: 38844796; NCT03336931). 38844796
RET M918T medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 malignant pheochromocytoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in stable disease with progression-free survival for at least 56.3 months in a patient with metastatic pheochromocytoma harboring somatic RET M918T and resulted in a complete response by IRC assessment and partial response by investigator assessment in a second patient with concomitant pheochromocytoma and medullary thyroid carcinoma harboring germline RET M918T (PMID: 38661071;NCT03157128). 38661071
RET M918T Advanced Solid Tumor sensitive 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 Advanced Solid Tumor sensitive 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 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 Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET M918T in culture (PMID: 36166639). 36166639
RET M918T Advanced Solid Tumor predicted - sensitive 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 Vepafestinib Preclinical - Cell culture Actionable In a preclinical study, Vepafestinib (TAS0953/HM06) inhibited proliferation of cells expressing RET M918T in culture (PMID: 37743366). 37743366
RET M918T Advanced Solid Tumor predicted - sensitive 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 predicted - sensitive FHND5071 Preclinical - Cell culture Actionable In a preclinical study, FHND5071 inhibited Ret phosphorylation and proliferation in cells expressing RET M918T in culture (Cancer Res (2023) 83 (8_Supplement): LB330). detail...
RET M918T medullary thyroid carcinoma sensitive MitoQ + Selpercatinib Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Retevmo (selpercatinib) and MitoQ resulted in a partial response in a patient with medullary thyroid cancer harboring RET M918T, and in preclinical analysis, synergistically inhibited viability of a medullary thyroid cancer cell line harboring RET M918T in culture (PMID: 38378752). 38378752
RET M918T medullary thyroid carcinoma sensitive SY-5007 Phase I Actionable In a Phase I trial, SY-5007 treatment demonstrated safety and resulted in an objective response rate (ORR) of 57.8% (67/116, partial responses), a disease control rate (DCR) of 95.7% (111/116), and a median progression-free survival of 21.1 mo in advanced solid tumor patients harboring RET fusions or alterations, with an ORR of 52.2% (12/23) and DCR of 91.3% (21/23) at the phase II dose in medullary thyroid cancer patients harboring RET M918T (n=15) or other mutations (n=8) (PMID: 39489747; NCT05278364). 39489747
ATM L804fs ATM S978fs RET M918T medullary thyroid 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 G810S RET M918T Advanced Solid Tumor predicted - sensitive TY-1091 Preclinical - Biochemical Actionable In a preclinical study, TY-1091 inhibited activity in a cell line expressing RET G810S and M918T in culture (Cancer Res (2023) 83 (7_Supplement): 3419). detail...
RET Y806C RET M918T medullary thyroid carcinoma predicted - resistant Pralsetinib Case Reports/Case Series Actionable In a retrospective analysis, a medullary thyroid carcinoma patient harboring RET M918T progressed on treatment with Gavreto (pralsetinib) and was found to have acquired RET Y806C (PMID: 38127829; NCT03157128, NCT03037385, NCT03780517). 38127829
RET Y806C RET M918T medullary thyroid carcinoma predicted - resistant Selpercatinib Case Reports/Case Series Actionable In a retrospective analysis, a medullary thyroid carcinoma patient harboring RET M918T progressed on treatment with Retevmo (selpercatinib) and was found to have acquired RET Y806C (PMID: 38127829; NCT03157128, NCT03037385, NCT03780517). 38127829
RET G810N RET M918T medullary thyroid carcinoma predicted - resistant Selpercatinib Case Reports/Case Series Actionable In a retrospective analysis, a medullary thyroid carcinoma patient harboring RET M918T progressed on treatment with Retevmo (selpercatinib) and was found to have acquired RET G810N (PMID: 38127829; NCT03157128, NCT03037385, NCT03780517). 38127829
RET S891A Advanced Solid Tumor sensitive 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 Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation in cells expressing RET S891A in culture (PMID: 17664273). 17664273
RET S891A medullary thyroid carcinoma predicted - sensitive Vandetanib Case Reports/Case Series Actionable In a clinical case study, neoadjuvant Caprelsa (vandetanib) treatment resulted in a 65% decrease in the thyroid mass and cervical lymph nodes allowing for surgical resection in a pediatric patient with medullary thyroid carcinoma harboring RET S891A (PMID: 38207224). 38207224
RET S891A Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET S891A in culture (PMID: 15184865). 15184865
RET C634W thyroid 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 cancer sensitive 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 carcinoma sensitive 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 cancer sensitive 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 carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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
RET C634W medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive 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 medullary thyroid carcinoma sensitive Vepafestinib Preclinical - Cell culture Actionable In a preclinical study, Vepafestinib (TAS0953/HM06) inhibited proliferation of a medullary thyroid cancer cell line harboring RET C634W in culture (PMID: 37743366). 37743366
RET C634W thyroid cancer predicted - sensitive 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 cancer predicted - sensitive TY-1091 Preclinical - Cell line xenograft Actionable In a preclinical study, TY-1091 inhibited proliferation in a thyroid cancer cell line harboring RET C634W in culture and inhibited tumor growth in a cell line xenograft model (Cancer Res (2023) 83 (7_Supplement): 3419). detail...
RET C634W medullary thyroid carcinoma sensitive MitoQ + Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Retevmo (selpercatinib) and MitoQ synergistically inhibited viability of a medullary thyroid cancer cell line harboring RET C634W in culture (PMID: 38378752). 38378752
RET C634W Advanced Solid Tumor sensitive SY-5007 Preclinical - Cell culture Actionable In a preclinical study, SY-5007 inhibited proliferation in cells expressing RET C634W in culture (PMID: 39489747). 39489747
RET C618R medullary thyroid carcinoma predicted - sensitive Sorafenib Case Reports/Case Series 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; NCT00390325). 20368568
RET C634Y Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of transformed cells harboring RET C634Y in culture (PMID: 23526464). 23526464
RET C634Y medullary thyroid carcinoma predicted - sensitive Sorafenib Case Reports/Case Series 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; NCT00390325). 20368568
RET C634Y Advanced Solid Tumor sensitive 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 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 C634Y Advanced Solid Tumor sensitive 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 E768D Advanced Solid Tumor sensitive 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 E768D Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET E768D in culture (PMID: 15184865). 15184865
RET E632_L633del Advanced Solid Tumor conflicting Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing RET E632_L633del was less sensitive to Gavreto (pralsetinib) than cells expressing wild-type RET in culture (PMID: 36416226). 36416226
RET E632_L633del Advanced Solid Tumor conflicting Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET E632_L633del in culture (PMID: 36166639). 36166639
RET E632_L633del medullary thyroid carcinoma conflicting Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in limited activity in a patient with medullary thyroid carcinoma harboring RET E632_L633del, with a partial response achieved at cycle 9 but significant progressive disease observed at cycle 13 (PMID: 36416226; NCT03157128). 36416226
RET E632_L633del medullary thyroid carcinoma conflicting Selpercatinib Case Reports/Case Series Actionable In a Phase I trial, Retevmo (selpercatinib) resulted in a partial response in the target lesions and stable disease in the non-target lesions in a patient with sporadic medullary thyroid cancer harboring RET E632_L633del, and treatment continued for at least 17 months (PMID: 35616103; NCT03906331). 35616103
RET E632_L633del Advanced Solid Tumor conflicting Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing RET E632_L633del was less sensitive to Retevmo (selpercatinib) than cells expressing wild-type RET in culture (PMID: 36416226). 36416226
RET E632_L633del Advanced Solid Tumor conflicting Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET E632_L633del in culture (PMID: 36166639). 36166639
RET C634F medullary thyroid carcinoma predicted - sensitive Sorafenib Case Reports/Case Series 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; NCT00390325). 20368568
RET C634F malignant pheochromocytoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in a partial response with treatment lasting 37 months in a patient with metastatic pheochromocytoma harboring germline RET C634F (PMID: 38661071; NCT03157128). 38661071
RET C620R medullary thyroid carcinoma predicted - sensitive Everolimus Case Reports/Case Series 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 harboring a RET C620R mutation (PMID: 26294908; NCT01118065). 26294908
RET C620R Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET C620R in culture (PMID: 36166639). 36166639
RET C620R Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET C620R in culture (PMID: 36166639). 36166639
HRAS A59T RET A883F RET A883T medullary thyroid carcinoma predicted - resistant Pralsetinib Case Reports/Case Series Actionable In a retrospective analysis, a medullary thyroid carcinoma patient harboring RET A883T progressed on treatment with Gavreto (pralsetinib) and was found to have acquired RET A883F and HRAS A59T (PMID: 38127829; NCT03157128, NCT03037385, NCT03780517). 38127829
RET L790F Advanced Solid Tumor sensitive 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 Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET L790F in culture (PMID: 15184865). 15184865
RET L790F medullary thyroid carcinoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a partial response in a pediatric patient with medullary thyroid carcinoma harboring RET L790F (PMID: 38844796; NCT03336931). 38844796
RET A883F Advanced Solid Tumor sensitive 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 Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET A883F in culture (PMID: 15184865). 15184865
RET D898V Advanced Solid Tumor sensitive 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 Y806C Advanced Solid Tumor sensitive 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 E884K Advanced Solid Tumor sensitive 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 over exp Advanced Solid Tumor predicted - sensitive 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 over exp breast cancer sensitive 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 pulmonary neuroendocrine tumor predicted - sensitive Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited proliferation of a lung neuroendocrine tumor cell line with high RET expression in 3D spheroid culture (Cancer Res (2023) 83 (7_Supplement): 4039). detail...
RET over exp pulmonary neuroendocrine tumor predicted - sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited proliferation of a lung neuroendocrine tumor cell line with high RET expression in 3D spheroid culture (Cancer Res (2023) 83 (7_Supplement): 4039). detail...
RET D631Y Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET D631Y in culture (PMID: 36166639). 36166639
RET D631Y Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET D631Y in culture (PMID: 36166639). 36166639
RET D631_L633delinsE Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET D631_L633delinsE in culture (PMID: 36166639). 36166639
RET D631_L633delinsE Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET D631_L633delinsE in culture (PMID: 36166639). 36166639
RET C620Y lung small cell carcinoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a partial response with rapid clinical improvement and shrinkage of brain, skin, and muscle metastases in a patient with small cell lung cancer harboring RET C620Y who remained on treatment after 6 months (PMID: 37922409). 37922409
RET C618S malignant pheochromocytoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in a partial response lasting 3.8 months in a patient with metastatic pheochromocytoma harboring RET C618S (PMID: 38661071; NCT03157128). 38661071
RET A883X medullary thyroid 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 M918X medullary thyroid 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...
RET C609X medullary thyroid 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 C611X medullary thyroid 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 C618X medullary thyroid 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 C620X medullary thyroid 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 C634X medullary thyroid 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 medullary thyroid carcinoma sensitive 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 E768X medullary thyroid 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 L790X medullary thyroid 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 Y791X medullary thyroid 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 V804X medullary thyroid 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 medullary thyroid carcinoma sensitive 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 S891X medullary thyroid 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 C630X medullary thyroid 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 L629P RET D631_R635delinsG RET V637R medullary thyroid carcinoma predicted - sensitive 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 V804E Advanced Solid Tumor predicted - sensitive 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 V804E Advanced Solid Tumor predicted - sensitive TY-1091 Preclinical - Biochemical Actionable In a preclinical study, TY-1091 inhibited activity in a cell line expressing RET V804E in culture (Cancer Res (2023) 83 (7_Supplement): 3419). detail...
RET G810S Advanced Solid Tumor predicted - sensitive 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 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 G810S Advanced Solid Tumor predicted - sensitive TY-1091 Preclinical - Cell culture Actionable In a preclinical study, TY-1091 inhibited activity in a cell line expressing RET G810S in culture (Cancer Res (2023) 83 (7_Supplement): 3419). detail...
RET G810R Advanced Solid Tumor predicted - sensitive 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 G810R Advanced Solid Tumor predicted - sensitive 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 G810C Advanced Solid Tumor predicted - sensitive 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 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 R886W Advanced Solid Tumor sensitive 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 D378_G385delinsE medullary thyroid carcinoma predicted - sensitive Vandetanib Case Reports/Case Series Actionable In a clinical case study, Caprelsa (vandetanib) treatment resulted in an ongoing biochemical response for more than 6 months in a pediatric patient 16 years old with metastatic medullary thyroid carcinoma harboring RET D378_G385delinsE (PMID: 28209747). 28209747
RET D378_G385delinsE medullary thyroid carcinoma predicted - sensitive 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
EML4 - RET lung adenocarcinoma conflicting Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, a patient-derived lung adenocarcinoma cell line harboring EML4-RET was resistant to treatment with Mekinist (trametinib), demonstrating decreased cell proliferation in culture, but led to delayed tumor growth in a cell line xenograft model (PMID: 33795352). 33795352
EML4 - RET lung adenocarcinoma predicted - sensitive Ponatinib Preclinical - Patient cell culture Actionable In a preclinical study, Iclusig (ponatinib) treatment induced apoptosis in a patient-derived lung adenocarcinoma cell line harboring EML4-RET in culture (PMID: 33795352). 33795352
EML4 - RET lung adenocarcinoma predicted - sensitive Volasertib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived lung adenocarcinoma cell line harboring EML4-RET was moderately sensitive to treatment with Volasertib (BI 6727) in culture (PMID: 33795352). 33795352
EML4 - RET lung adenocarcinoma sensitive RXDX-105 Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived lung adenocarcinoma cell line harboring EML4-RET was sensitive to treatment with Agerafenib (RXDX-105) in culture, demonstrating decreased Akt phosphorylation and induction of apoptosis (PMID: 33795352). 33795352
EML4 - RET lung adenocarcinoma sensitive Pralsetinib Preclinical - Cell line xenograft Actionable In a preclinical study, a patient-derived lung adenocarcinoma cell line harboring EML4-RET was sensitive to treatment with Gavreto (pralsetinib), demonstrating decreased cell proliferation in culture, and inhibition of tumor growth in a xenograft model (PMID: 33795352). 33795352
EML4 - RET lung adenocarcinoma no benefit RXDX-105 + Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, the addition of Mekinist (trametinib) did not increase sensitivity to Agerafenib (RXDX-105) treatment in a patient-derived lung adenocarcinoma cell line harboring EML4-RET in culture (PMID: 33795352). 33795352
EML4 - RET lung adenocarcinoma predicted - sensitive GSK2126458 + RXDX-105 Preclinical - Patient cell culture Actionable In a preclinical study, the addition of Omipalisib (GSK2126458) resulted in increased sensitivity to Agerafenib (RXDX-105) treatment in a patient-derived lung adenocarcinoma cell line harboring EML4-RET in culture (PMID: 33795352). 33795352
RET D571N Advanced Solid Tumor sensitive Pralsetinib Preclinical - Biochemical Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling in transformed cells expressing RET D571N in culture (PMID: 36166639). 36166639
RET D571N Advanced Solid Tumor sensitive Selpercatinib Preclinical - Biochemical Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling in transformed cells expressing RET D571N in culture (PMID: 36166639). 36166639
RET T930K Advanced Solid Tumor sensitive 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 T930K Advanced Solid Tumor sensitive 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 T930P Advanced Solid Tumor sensitive 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 T930P Advanced Solid Tumor sensitive 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 D898_E901del medullary thyroid carcinoma predicted - resistant Vandetanib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del demonstrated primary resistance to Caprelsa (vandetanib) treatment (PMID: 37535881). 37535881
RET D898_E901del Advanced Solid Tumor predicted - sensitive Vandetanib Preclinical - Cell culture Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET D898_E901del, but to a lesser degree than cells expressing RET C634R in culture (PMID: 37535881). 37535881
RET D898_E901del Advanced Solid Tumor resistant Cabozantinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing RET D898_E901del were resistant to Cometriq (Cabometyx, cabozantinib) in culture (PMID: 37535881). 37535881
RET D898_E901del Advanced Solid Tumor sensitive 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 D898_E901del medullary thyroid carcinoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a clinical case study, Retevmo (selpercatinib) treatment resulted in a 61% reduction in the sum of the diameters of the target lesions in a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del, with treatment lasting 1 year (PMID: 37535881). 37535881
RET D898_E901del medullary thyroid carcinoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in a clinical response after one month, with a partial response in liver lesions and abdominal lymph nodes that was maintained for 24 months, in a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del (PMID: 38438731; NCT03157128). 38438731
RET D898_E901del Advanced Solid Tumor sensitive 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 Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET D898_E901del in culture (PMID: 37535881). 37535881
RET D631_L633delinsS medullary thyroid carcinoma predicted - sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I trial, Retevmo (selpercatinib) resulted in stable disease in the target lesions and a partial response in the non-target lesions in a patient with sporadic medullary thyroid cancer harboring RET D631_L633delinsS (PMID: 35616103; NCT03906331). 35616103
RET C630del Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) treatment inhibited Ret phosphorylation and downstream signaling and resulted in decreased cell viability and colony formation in cells expressing RET C630del in culture (PMID: 35689816). 35689816
RET V591_G607del RET L1016S medullary thyroid carcinoma predicted - sensitive Pralsetinib Case Reports/Case Series Actionable In a clinical case study, Gavreto (pralsetinib) treatment resulted in a partial response lasting more than 1 year in a patient with medullary thyroid carcinoma harboring RET V591_G607del and germline RET L1016S (PMID: 36053791). 36053791
RET D567N Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and viability in transformed cells expressing RET D567N in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639). 36166639
RET D567N Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling and viability in transformed cells expressing RET D567N in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639). 36166639
RET D567Y Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling and viability in transformed cells expressing RET D567Y in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639). 36166639
RET D567Y Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling and viability in transformed cells expressing RET D567Y in culture and inhibited tumor growth in a cell line xenograft model (PMID: 36166639). 36166639
RET D584N Advanced Solid Tumor sensitive Pralsetinib Preclinical - Biochemical Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling in transformed cells expressing RET D584N in culture (PMID: 36166639). 36166639
RET D584N Advanced Solid Tumor sensitive Selpercatinib Preclinical - Biochemical Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling in transformed cells expressing RET D584N in culture (PMID: 36166639). 36166639
RET G607C Advanced Solid Tumor sensitive Pralsetinib Preclinical - Cell culture Actionable In a preclinical study, Gavreto (pralsetinib) inhibited viability in transformed cells expressing RET G607C in culture (PMID: 36166639). 36166639
RET G607C Advanced Solid Tumor sensitive Selpercatinib Preclinical - Cell culture Actionable In a preclinical study, Retevmo (selpercatinib) inhibited viability in transformed cells expressing RET G607C in culture (PMID: 36166639). 36166639
RET E574D Advanced Solid Tumor sensitive Pralsetinib Preclinical - Biochemical Actionable In a preclinical study, Gavreto (pralsetinib) inhibited Ret signaling in transformed cells expressing RET E574D in culture (PMID: 36166639). 36166639
RET E574D Advanced Solid Tumor sensitive Selpercatinib Preclinical - Biochemical Actionable In a preclinical study, Retevmo (selpercatinib) inhibited Ret signaling in transformed cells expressing RET E574D in culture (PMID: 36166639). 36166639
RET L633_A639del medullary thyroid carcinoma predicted - sensitive Vandetanib Case Reports/Case Series Actionable In a clinical case study, Caprelsa (vandetanib) treatment resulted in disease stabilization in a patient with metastatic medullary thyroid carcinoma harboring RET L633_A639del (PMID: 28209747). 28209747