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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 Erk phosphorylation in cultured cells (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 | |
Category Variants Paths |
EML4 mutant EML4 fusion EML4 - RET RET mutant RET act mut EML4 - RET RET mutant RET rearrange RET fusion EML4 - RET |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 |