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Gene EML4 RET
Variant EML4 - RET
Impact List fusion
Protein Effect gain of function - predicted
Gene Variant Descriptions EML4-RET results from the fusion of EML4 and RET (PMID: 33082208), which results in increased Met and Erk phosphorylation (PMID: 33848463), and therefore, is predicted to lead to a gain of protein function. EML4-RET has been identified in lung cancer (PMID: 33082208, PMID: 31485557, PMID: 30487236).
Associated Drug Resistance

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Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 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
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 thyroid gland medullary carcinoma sensitive Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55), with five complete and 33 partial responses, in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations who were previously treated, while patients who had not been previously treated demonstrated an ORR of 73% (64/88), with ten complete and 54 partial responses (PMID: 32846061; NCT03157128). detail... 32846061
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant 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 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 thyroid gland medullary carcinoma 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 60% (3/55) in patients with advanced or metastatic medullary thyroid cancer harboring RET mutations who received prior treatments, ORR was 60% (32/53) in patients with prior therapies and 71% (15/21) in treatment-naive patients (PMID: 34118198; NCT03037385). 34118198 detail...
RET mutant thyroid gland medullary 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 thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908). 26294908
RET mutant 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 thyroid gland medullary 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 fusion thyroid gland papillary 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 thyroid gland papillary 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 thyroid gland medullary 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 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 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 thyroid gland anaplastic 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 gallbladder cancer sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) or subsequent-line therapy (category 2B) for patients with unresectable or metastatic gallbladder cancer harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland anaplastic 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 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 differentiated thyroid gland 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 thyroid gland follicular 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 differentiated thyroid gland 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 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 thyroid gland cancer sensitive Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate of 79% (15/19), including one complete and 14 partial responses, with a median response duration of 18.4 months, and median progression-free survival of 20.1 months in adult and pediatric patients 12 years and older with RET fusion-positive thyroid cancer who were previously treated (PMID: 32846061; NCT03157128). detail... 32846061
RET fusion thyroid gland Hurthle cell carcinoma 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 lung non-small cell carcinoma sensitive Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 64% (64/105) in patients with RET fusion-positive non-small cell lung cancer, with a median duration of response of 17.5 months, ORR was 85% (33/39) and 91% (10/11) in previously treated patients and patients with measurable CNS metastasis, respectively (PMID: 32846060; NCT03157128). detail... 32846060
RET fusion 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 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 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 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 intrahepatic cholangiocarcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) or subsequent-line therapy (category 2B) for patients with unresectable or metastatic intrahepatic cholangiocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion extrahepatic bile duct carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as primary (category 2B) or subsequent-line therapy (category 2B) for patients with unresectable or metastatic extrahepatic cholangiocarcinoma harboring RET fusions (NCCN.org). detail...
RET fusion thyroid gland Hurthle cell carcinoma 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 thyroid gland medullary 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 thyroid gland 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 thyroid gland follicular 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 Advanced Solid Tumor predicted - 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 60% (3/5) in patients with RET fusion positive advanced solid tumors other than thyroid cancer and non-small cell lung cancer (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion thyroid gland papillary 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 thyroid gland papillary carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with papillary thyroid carcinoma harboring RET fusions (NCCN.org). detail...
RET rearrange lung non-small cell carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines as a first-line therapy for non-small cell lung cancer patients with RET rearrangements (NCCN.org). detail...
RET rearrange lung 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 thyroid gland papillary 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 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 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 thyroid gland papillary 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 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 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 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 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 sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is in guidelines for non-small cell lung cancer patients with RET rearrangements (NCCN.org). detail...
RET rearrange lung non-small cell carcinoma sensitive Cabozantinib Guideline Actionable Cometriq (cabozantinib) is in guidelines for non-small cell lung cancer patients with RET rearrangements (NCCN.org). detail...
RET rearrange lung non-small cell carcinoma sensitive 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
Molecular Profile Protein Effect Treatment Approaches
EML4 - RET gain of function - predicted