Gene

RET

ret proto-oncogene

Explore in graph →CI-GENE-00023348HGNC:9967 ENSG00000165731 NCBI 5979 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (99)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 51–99 of 99 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
RET M918T5
Pralsetinib + SelpercatinibSubstitutes	Malignant NeoplasmALIAS	Predictive	D	Supports

Cohorts

Alteration frequency by cohort (117)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved117 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Colorectal Cancer (MSK, Cancer Discovery 2022) coadread_mskresistance_2022	Colorectal Adenocarcinoma	Ssm

Literature

Linked publications (30)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 30 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer.
· N Engl J Med · 2023 · PMID 37870969 · validated civic_curation pubmed
Efficacy of Selpercatinib in RET-Altered Thyroid Cancers.
· N Engl J Med · 2020 · PMID 32846061 · validated civic_curation pubmed
Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study.
· Lancet Oncol · 2021 · PMID 34118197 · validated civic_curation pubmed
Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study.
· Lancet Diabetes Endocrinol · 2021 · PMID 34118198 · validated civic_curation

RET G810S + RET M918T1
Selpercatinib	Thyroid Gland Medullary CarcinomaALIAS	Predictive	C	Supports Resistance	3	accepted	EID8196 In two out of three patients with MTC treated in a phase1/2 trial, the RET G810 mutation emerged in ctDNA together with an acquired resistance after initial response to selpercatinib. PMID 31988000 · Solomon et al., 2020 · Open in CIViC	civic

RET G810S + RET M918T1

Selpercatinib

Thyroid Gland Medullary CarcinomaALIAS

Predictive

Supports Resistance

accepted

EID8196

In two out of three patients with MTC treated in a phase1/2 trial, the RET G810 mutation emerged in ctDNA together with an acquired resistance after initial response to selpercatinib.

PMID 31988000 · Solomon et al., 2020 · Open in CIViC

RET Mutation6
(prognostic)	Thyroid Gland Medullary CarcinomaALIAS	Prognostic	B	Supports Poor Outcome	3	accepted	EID74 In a study of 100 patients with sporadic medullary thyroid carcinoma (MTC), RET gene exons 10-11 and 13-16 were analyzed with tumor and matched normal samples. A somatic RET mutation was identified in… (full text at CIViC) PMID 18073307 · Elisei et al., 2008 · Open in CIViC	civic
Cabozantinib	Thyroid Gland Medullary CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	submitted	EID8984 In this retrospective analysis of a phase 3 trial of cabozantinib or placebo in 330 patients. Among those, 51.2% were RET mutation-positive (38.2% with RET M918T), 34.8% were RET mutation-unknown, and… (full text at CIViC) PMID 27525386 · Sherman et al., 2016 · Open in CIViC	civic
NVP-AST487 + SapanisertibCombination	Thyroid Gland Carcinoma	Predictive	D	Supports Sensitivity Response	3	submitted	EID4854 The objective of this preclinical study was to investigate the contribution of mTOR activity to RET-induced signaling and cell growth and to establish whether growth suppression is enhanced by co-targ… (full text at CIViC) PMID 23828865 · Gild et al., 2013 · Open in CIViC	civic
Selpercatinib	Thyroid Gland Medullary CarcinomaALIAS	Predictive	A	Supports Sensitivity Response	5	accepted	EID12157 In this phase III trial, 291 patients (12 years or older) with medullary thyroid cancer harbouring RET mutations were enrolled. Patients were randomized in a 2:1 ratio to receive selpercatinib (n=193)… (full text at CIViC) PMID 37870969 · Hadoux et al., 2023 · Open in CIViC	civic
〃	Thyroid Gland Medullary CarcinomaALIAS	Predictive	A	Supports Sensitivity Response	4	accepted	EID8851 In this international phase 1/2 trial (NCT03157128), 55 RET-mutant medullary thyroid cancer patients who had previously received the multi-kinase inhibitors vandetanib and/or cabozantinib received th… (full text at CIViC) PMID 32846061 · Wirth et al., 2020 · Open in CIViC	civic
〃	Thyroid Gland Medullary CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	3	accepted	EID7070 In this phase 1 trial, patients with RET-fusion or mutation positive cancers were treated with the selective RET-inhibitor selpercatinib (LOXO-292). Tumor reduction was achieved in 79% of medullary th… (full text at CIViC) Open in CIViC	civic

RET Overexpression4
(prognostic)	Lung Adenocarcinoma	Prognostic	B	Supports Poor Outcome	3	accepted	EID7056 ASCL1 and RET mRNA levels were examined by microarray analysis in lung cancer samples. High expression of RET (RET-high) correlated with shorter overall survival compared to the RET-low group in patie… (full text at CIViC) PMID 24037524 · Kosari et al., 2014 · Open in CIViC	civic
Sunitinib	Papillary Adenocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID1518 A 78-year-old man presented with oral papillary adenocarcinoma and lung metastases that were refractory to standard treatment. Tumor sequencing showed increased MAPK activity due to RET over-expressi… (full text at CIViC) PMID 20696054 · Jones et al., 2010 · Open in CIViC	civic
Vandetanib	Estrogen Receptor-negative Breast CancerUNRESOLVED	Predictive	D	Supports Sensitivity Response	3	submitted	EID2992 The activity of Vandetanib was tested in vivo in three PDX models of TNBC and one model of HER2+ BC with different expression levels of RET and EGFR. Vandetanib induced tumor regression in PDX models … (full text at CIViC) PMID 26686064 · Hatem et al., 2016 · Open in CIViC	civic
〃	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	2	accepted	EID740 Vandetanib was tested in 4 murine models of patient-derived xenografts. In xenografts with high expression of EGFR or RET, vandetanib led to tumor regression, in those without high expression, vandeta… (full text at CIViC) PMID 26686064 · Hatem et al., 2016 · Open in CIViC	civic

RET T930K2
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	3	submitted	EID11864 To assess recurrent somatic mutations in the RET kinase domain (T930K/M/P and D898_E901del) that were identified in a large study of 37,056 Chinese cancer patients, in vitro functional tests were run … (full text at CIViC) PMID 32284345 · Zhao et al., 2020 · Open in CIViC	civic
Pralsetinib + SelpercatinibSubstitutes	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	submitted	EID11869 Ba/F3 transformed cells harboring RET D898_E901del, T930K, T930P, or M918T mutations were shown to be sensitive to the highly selective RET inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667… (full text at CIViC) PMID 32284345 · Zhao et al., 2020 · Open in CIViC	civic

RET V804M3
Dasatinib	Chronic Myeloid Leukemia, BCR-ABL1 PositiveALIAS	Predictive	D	Supports Resistance	2	submitted	EID7516 In an in vitro kinase study, the recombinant RET V804M mutant kinase demonstrated resistance to dasatinib treatment at concentrations of 1μM and 10μM (activity %: 99 and 87) when compared to wild type… (full text at CIViC) PMID 19039322 · Remsing Rix et al., 2009 · Open in CIViC	civic
Selpercatinib	Thyroid Gland Medullary CarcinomaALIAS	Predictive	C	Supports Sensitivity Response	4	submitted	EID6951 A patient with RET M918T-mutant medullary thyroid cancer metastatic to the liver and an acquired RET V804M gatekeeper resistance mutation, previously treated with six MKI regimens, experienced rapid r… (full text at CIViC) PMID 29912274 · Subbiah et al., 2018 · Open in CIViC	civic
〃	Thyroid Gland Medullary CarcinomaALIAS	Predictive	C	Supports Sensitivity Response	3	accepted	EID7068 In this phase 1 trial, 57 patients were treated with the selective RET Inhibitor selpercatinib (LOXO-292). A 57-year-old male with a hereditary RET V804M gatekeeper mutation treated with 3 prior multi… (full text at CIViC) Open in CIViC	civic

RET Fusion15
Alectinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	accepted	EID4850 Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. 4 patients with metastatic RET-rearranged NSCLC were identified. 3 of 4 had receive… (full text at CIViC) PMID 27544060 · Lin et al., 2016 · Open in CIViC	civic
Cabozantinib	Lung Adenocarcinoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID4847 RET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with … (full text at CIViC) PMID 27825636 · Drilon et al., 2016 · Open in CIViC	civic
Pralsetinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	accepted	EID11233 In an open-label, phase 1/2 trial on 87 patients with NSCLC including RET-fusion were given 400 mg once-daily oral pralsetinib, with the outcome measured as overall response rate. Overall responses we… (full text at CIViC) PMID 34118197 · Gainor et al., 2021 · Open in CIViC	civic
〃	Malignant Thyroid Gland Neoplasm	Predictive	A	Supports Sensitivity Response	4	accepted	EID11234 In a phase 1/2, open-label trial, 122 patients with RET-mutant medullary cancer and 20 with RET-fusion positive thyroid cancer were administered 400 mg daily oral pralsetinib. The overall response rat… (full text at CIViC) PMID 34118198 · Subbiah et al., 2021 · Open in CIViC	civic
〃	Solid NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	submitted	EID11266 In the phase 1/2 clinical trial NCT03037385, one arm assessed the therapeutic benefit of the selective RET inhibitor pralsetinib across a range RET fusion positive solid tumors, excluding NSCLC and th… (full text at CIViC) PMID 35962206 · Subbiah et al., 2022 · Open in CIViC	civic
Selpercatinib	Malignant Thyroid Gland Neoplasm	Predictive	A	Supports Sensitivity Response	4	accepted	EID8852 In this phase 1/2 trial (NCT03157128), patients with RET altered thyroid cancers were enrolled to receive the highly selective RET inhibitor selpercatinib. Among 19 patients with previously treated RE… (full text at CIViC) PMID 32846061 · Wirth et al., 2020 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	submitted	EID11318 In a follow up publication on the NCT03157128 clinical trial, results of 316 RET fusion positive NSCLC patients treated with the RET inhibitor selpercatinib were reported. Of note, this includes 144 … (full text at CIViC) PMID 36122315 · Drilon et al., 2023 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	accepted	EID7066 In this phase 1 trial, 57 patients with RET fusion- or mutation positive cancers were treated in 7 dose levels. Among patients with RET-Fusion positive NSCLC, objective response rates were 65% (n = 17… (full text at CIViC) Open in CIViC	civic
〃	Thyroid Gland Papillary CarcinomaALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID7069 In this phase 1 trial, patients with RET-fusion or mutation positive cancers were treated with the selective RET-inhibitor selpercatinib (LOXO-292). Among the 6 patients with RET-fusion positive papil… (full text at CIViC) Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	accepted	EID8850 Patients with RET-fusion positive non-small cell lung cancer were enrolled in this phase 1-2 trial of RET inhibitor selpercatinib. Among 105 consecutively enrolled patients who had previously received… (full text at CIViC) PMID 32846060 · Drilon et al., 2020 · Open in CIViC	civic
〃	Solid NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	submitted	EID12134 In this arm of the trial (LIBRETTO-001), the efficacy of selpercatinib was tested in 45 patients harbouring RET fusion-positive solid tumours (excluding lung or thyroid tumours). The objective respons… (full text at CIViC) PMID 36108661 · Subbiah et al., 2022 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	submitted	EID12135 In this arm of the trial (NCT03157128), the intracranial objective response rate (iORR) was assessed in 80 patients with RET fusion-positive non-small cell lung cancer (NSCLC) treated with selpercatin… (full text at CIViC) PMID 34088726 · Subbiah et al., 2021 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	submitted	EID6949 In a preclinical analysis, RET inhibitor LOXO-292 was active against RET-Fusion positive cell lines and xenograft models PMID 29912274 · Subbiah et al., 2018 · Open in CIViC	civic
Vandetanib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	accepted	EID4848 RET rearrangements involving RET are found in about 1% of NSCLC and define a unique molecular subset. This study was a multi-center, open-label, phase II clinical trial to examine the safety and effi… (full text at CIViC) PMID 27803005 · Lee et al., 2017 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	accepted	EID4849 We aimed to assess the efficacy and safety of vandetanib in patients with advanced RET-rearranged NSCLC. In this open-label, multicentre, phase 2 trial (LURET), patients with advanced RET-rearranged N… (full text at CIViC) PMID 27825616 · Yoh et al., 2017 · Open in CIViC	civic