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Profile Name EML4 - ALK
Gene Variant Detail

EML4 - ALK (gain of function)

Relevant Treatment Approaches ALK Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib + Sirolimus Preclinical Actionable In a preclinical study, transformed non-small cell lung cancer cells harboring EML4-ALK demonstrated enhanced growth inhibition to a combination treatment with Afinitor (sirolimus) and Ensartinib (X-396) (PMID: 21613408). 21613408
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells harboring EML4-ALK fusion, and reduced intracranial tumor size in cell line xenograft models (PMID: 26144315). 26144315
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK lung non-small cell carcinoma sensitive TAE226 Preclinical Actionable In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring EML4-ALK fusion in culture (PMID: 26090892). 26090892
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Entrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EML4-ALK were sensitive to Rozlytrek (entrectinib), resulting in inhibition of cell proliferation and complete tumor regression in cell line xenograft models (PMID: 26939704). 26939704
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 26698910). 26698910
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 26698910). 26698910
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Phase I Actionable In a Phase I trial, Xalkori (crizotinib) inhibited tumor growth by at least 30% from baseline in 90% (18/20) of patients with EML4-ALK positive non-small cell lung carcinoma (PMID: 20979469; NCT00585195). 20979469
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited phosphorylation of Alk and inhibited growth of human non-small cell lung cancer cell lines harboring EML4-ALK in culture (PMID: 25173427). 25173427
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited Alk phosphorylation and growth of a human non-small cell lung cancer cell line harboring EML4-ALK in culture and in cell line xenograft models (PMID: 21575866). 21575866
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Clinical Study - Cohort Actionable In a clinical study, non-small cell lung carcinoma patients harboring an EML4-ALK variant 1 (E13; A20, n=19) demonstrated a significantly longer progression-free survival (11.0 vs 4.2 months, p<0.05) compared to patients with a non-variant 1 EML4-ALK fusion (n=16) when treated with Xalkori (crizotinib) (PMID: 27354483). 27354483
EML4 - ALK neuroblastoma resistant ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing EML4-ALK in culture (PMID: 26554404). 26554404
EML4 - ALK neuroblastoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells harboring EML4-ALK in culture (PMID: 26554404). 26554404
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Afatinib + Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, combination of Gilotrif (afatinib) and Alecensa (alectinib) restored sensitivity to Alecensa (alectinib) in non-small cell lung cancer cells harboring EML4-ALK fusion that acquired resistance to Alecensa (alectinib) through up-regulating Egfr signaling in culture and inhibited tumor progression in cell line xenograft models (PMID: 26682573). 26682573
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited Alk phosphorylation and growth in non-small cell lung cancer cell lines harboring EML4-ALK in culture, and induced near complete tumor regression in cell line xenograft models (PMID: 27780853). 27780853
EML4 - ALK lung cancer sensitive ALK Inhibitor X-376 Preclinical - Cell line xenograft Actionable In a preclinical study, X-376 inhibited Alk signaling, resulted in growth inhibition in lung cancer cells harboring EML4-ALK fusion in culture and in cell line xenograft models (PMID: 21613408). 21613408
EML4 - ALK lung non-small cell carcinoma predicted - sensitive ALK Inhibitor Crizotinib + Filgotinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EML4-ALK in culture that had, over time, acquired resistance to Xalkori (crizotinib) showed decreased drug resistance when treatment was combined with Filgotinib (GLPG0634), demonstrating reduced expression of Osmr and phosphorylated-Stat3, and decreased cell viability (PMID: 28729401). 28729401
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor CEP-28122 Preclinical - Cell line xenograft Actionable In a preclinical study, CEP-28122 inhibited growth of non-small cell lung carcinoma cell lines harboring EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 22203728). 22203728
EML4 - ALK inflammatory myofibroblastic tumor predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with inflammatory myofibroblastic tumor harboring EML4-ALK achieved complete remission three years after starting Xalkori (crizotinib) treatment (PMID: 26808369). 26808369
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191). 30002191
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Ensartinib Preclinical - Cell culture Actionable In a preclinical study, Ensartinib (X-396) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191). 30002191
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Repotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Augtyro (repotrectinib) inhibited growth of transformed cells expressing EML4-ALK in culture, led to tumor growth inhibition in cell line xenograft models (PMID: 30093503). 30093503
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Iruplinalkib Preclinical - Cell culture Actionable In a preclinical study, Iruplinalkib (WX-0593) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 35421578). 35421578
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Iruplinalkib Preclinical - Pdx Actionable In a preclinical study, Iruplinalkib (WX-0593) inhibited tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK (PMID: 35421578). 35421578
EML4 - ALK lung non-small cell carcinoma sensitive MTI-31 Preclinical - Cell line xenograft Actionable In a preclinical study, MTI-31 inhibited proliferation and migration and increased PD-L1 degradation in a non-small cell lung cancer cell line harboring EML4-ALK in culture, and inhibited tumor growth in xenograft models (PMID: 30796032). 30796032
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Ensartinib Phase II Actionable In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 59% (41/70; all partial responses) and stable disease in 31% (22/70) of patients with crizotinib-refractory non-small cell lung cancer harboring EML4-ALK (PMID: 31628085; NCT03215693). 31628085
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK variant 8 achieved a pathologic complete response following treatment with Xalkori (crizotinib), with a reduction in primary tumor size and pleural metastases within 1 month of treatment, and continuation of treatment for 5 years until death, after which cancer was not observed at autopsy (PMID: 31690489). 31690489
EML4 - ALK Advanced Solid Tumor sensitive Taletrectinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing EML4-ALK were sensitive to treatment with Taletrectinib (DS6051b) in culture, demonstrating cell growth inhibition (PMID: 31399568). 31399568
EML4 - ALK breast cancer sensitive ALK Inhibitor Ceritinib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing EML4-ALK were sensitive to treatment with Zykadia (ceritinib) in culture, demonstrating inhibition of cell growth (PMID: 32348852). 32348852
EML4 - ALK breast cancer resistant Fulvestrant Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing EML4-ALK demonstrated resistance to treatment with Faslodex (fulvestrant) in culture (PMID: 32348852). 32348852
EML4 - ALK breast cancer predicted - sensitive ALK Inhibitor Ceritinib + Fulvestrant Preclinical - Cell culture Actionable In a preclinical study, the addition of Zykadia (ceritinib) to Faslodex (fulvestrant) treatment in breast cancer cells expressing EML4-ALK restored growth inhibition in culture (PMID: 32348852). 32348852
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK lung adenocarcinoma sensitive Alvocidib Preclinical - Cell line xenograft Actionable In a preclinical study, Alvocidib (flavopiridol) treatment induced cell cycle arrest and apoptosis, reduced viability, and inhibited proliferation in both a parental lung adenocarcinoma cell line and isogenic lung adenocarcinoma cell lines resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib), all harboring EML4-ALK, in culture, and reduced tumor growth in Xalkori (crizotinib) and Alecensa (alectinib)-resistant cell line xenograft models (PMID: 32558295). 32558295
EML4 - ALK lung adenocarcinoma sensitive Dinaciclib Preclinical - Cell culture Actionable In a preclinical study, Dinaciclib (SCH 727965) treatment induced apoptosis, reduced viability, and inhibited proliferation in parental lung adenocarcinoma cells, and isogenic cells resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib), all harboring EML4-ALK in culture (PMID: 32558295). 32558295
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Alvocidib + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Alvocidib (flavopiridol) treatment in combination with Xalkori (crizotinib) reduced viability of Xalkori (crizotinib)-resistant lung adenocarcinoma cells harboring EML4-ALK in culture, but did not result in synergistic effects (PMID: 32558295). 32558295
EML4 - ALK lung adenocarcinoma sensitive THZ1 Preclinical - Cell culture Actionable In a preclinical study, THZ1 treatment reduced viability and inhibited proliferation of parental lung adenocarcinoma, and isogenic cells resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib) cells, all harboring EML4-ALK, in culture (PMID: 32558295). 32558295
EML4 - ALK lung cancer predicted - sensitive ALK Inhibitor Bevacizumab + Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a lung cancer patient with brain metastases harboring EML4-ALK who had developed resistance to treatment with Lorbrena (lorlatinib) after three months was subsequently treated with a combination of Avastin (bevacizumab) and Lorbrena (lorlatinib), and demonstrated a best response of stable disease, including disease control for 5.4 months, and 8% tumor shrinkage in the brain (PMID: 33283131). 33283131
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 33627640). 33627640
EML4 - ALK Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 33627640). 33627640
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib + SHP099 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Alecensa (alectinib) and SHP099 inhibited downstream signaling and synergistically inhibited proliferation in non-small cell lung cancer cell lines harboring EML4-ALK in culture, and resulted in increased suppression of tumor growth in cell line xenograft models compared to either agent alone (PMID: 34158345). 34158345
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Alecensa (alectinib) and Koselugo (selumetinib) inhibited tumor growth in cell line xenograft models of non-small cell lung cancer harboring EML4-ALK, but was less potent compared to treatment with the combination of Alecensa (alectinib) and SHP099 (PMID: 34158345). 34158345
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Alectinib + RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, the combination of Alecensa (alectinib) and RMC-4550 inhibited cell growth and downstream signaling in non-small cell lung cancer cell lines harboring EML4-ALK in culture (PMID: 34158345). 34158345
EML4 - ALK colorectal carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in rapid clinical benefit and a partial response after 1 month of therapy in a patient with metastatic colorectal carcinoma harboring EML4-ALK, until disease progression after 4 months (PMID: 34036227). 34036227
EML4 - ALK colorectal carcinoma predicted - sensitive ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical benefit and a progression-free survival of 11.5 months in a patient with metastatic colorectal carcinoma harboring EML4-ALK, whose disease progressed on initial Xalkori (crizotinib) treatment and did not respond to subsequent Alecensa (alectinib) treatment (PMID: 34036227). 34036227
EML4 - ALK papillary renal cell carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical study, three previously treated patients with metastatic papillary renal cell carcinoma harboring an EML4-ALK fusion were sensitive to treatment with Alecensa (alectinib), demonstrating a clinical and radiographic response in one patient, a radiographic response and ongoing stable disease for 9 months in another patient, and regression of multiple metastatic sites in the third patient (PMID: 29685646). 29685646
EML4 - ALK Advanced Solid Tumor predicted - sensitive ALK Inhibitor NUV-655 Preclinical - Cell culture Actionable In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). detail...
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling, induced apoptosis, and inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 34845836). 34845836
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor XMU-MP-5 Preclinical - Cell line xenograft Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling, induced apoptosis, and inhibited proliferation of non-small cell lung caner cells harboring EML4-ALK in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836). 34845836
EML4 - ALK large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in significant clinical improvement and a partial response in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK after 4 weeks of therapy, however, progression in bone metastasis developed at 4 months (PMID: 34994612). 34994612
EML4 - ALK colon adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in clinical improvement after 1 month and a partial response lasting 8 months in a patient with colon adenocarcinoma harboring EML4-ALK (PMID: 33776709). 33776709
EML4 - ALK pancreatic cancer predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in stable primary disease and decrease in brain lesions with treatment lasting nearly 10 months before progression of the brain metastases in a patient with pancreatic cancer harboring EML4-ALK (PMID: 34568053). 34568053
EML4 - ALK pancreatic cancer predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in tumor shrinkage with treatment lasting eight months in a patient with pancreatic cancer harboring EML4-ALK (PMID: 34568053). 34568053
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 17.5 months in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 34911818). 34911818
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in a partial response lasting 8.7 months in a patient with lung adenocarcinoma harboring EML4-ALK, who progressed on prior Alecensa (alectinib) treatment (PMID: 34911818). 34911818
EML4 - ALK lung adenocarcinoma sensitive ALK Inhibitor Lorlatinib Preclinical - Pdx Actionable In a preclinical study, Lorbrena (lorlatinib) treatment decreased tumor growth in a patient-derived xenograft (PDX) model of lung adenocarcinoma harboring EML4-ALK (PMID: 34911818). 34911818
EML4 - ALK lung adenocarcinoma sensitive ALK Inhibitor Brigatinib Preclinical - Pdx Actionable In a preclinical study, Alunbrig (brigatinib) treatment decreased tumor growth in a patient-derived xenograft (PDX) model of lung adenocarcinoma harboring EML4-ALK (PMID: 34911818). 34911818
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 35421578). 35421578
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 6.5 months in a patient with lung adenocarcinoma harboring EML4-ALK, who also harbored IDH1 R132H (PMID: 35324529). 35324529
EML4 - ALK lung cancer predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response in a patient with metastatic lung cancer harboring EML4-ALK (PMID: 34378333). 34378333
EML4 - ALK lung squamous cell carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment with whole-brain radiotherapy resulted in a partial response with a progression-free survival of 17 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK (PMID: 34376997). 34376997
EML4 - ALK lung squamous cell carcinoma predicted - sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a complete response in the lung and partial response in the brain lesions in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, with a progression-free survival of 11 months (PMID: 34376997). 34376997
EML4 - ALK lung squamous cell carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 9.5 months in a patient with metastatic squamous cell lung cancer harboring EML4-ALK (PMID: 34324792). 34324792
EML4 - ALK ovarian serous carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in decreased CA-125 and complete remission lasting more than 1 year in a patient with metastatic high-grade serous ovarian cancer harboring EML4-ALK (E13:E20), who previously progressed on chemotherapy (PMID: 32845005). 32845005
EML4 - ALK malignant pleural mesothelioma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in symptom improvement and a partial response lasting 3.5 months in a patient with malignant pleural mesothelioma harboring EML4-ALK (PMID: 32600123). 32600123
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor TQ-B3139 Preclinical - Cell line xenograft Actionable In a preclinical study, TQ-B3139 (CT-711) inhibited Alk signaling and proliferation and induced cell cycle arrest and apoptosis in non-small cell lung cancer cell lines harboring EML4-ALK in culture and induced tumor regression in cell line xenograft models (PMID: 30210922). 30210922
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor TQ-B3139 Preclinical - Cell line xenograft Actionable In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922). 30210922
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor APG-2449 Preclinical - Cell culture Actionable In a preclinical study, APG-2449 inhibited proliferation of cells expressing EML4-ALK in culture (PMID: 35820889). 35820889
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor APG-2449 Preclinical - Cell line xenograft Actionable In a preclinical study, APG-2449 inhibited proliferation of non-small cell lung cancer cell lines harboring EML4-ALK in culture and resulted in dose-dependent antitumor activity in a cell line xenograft model (PMID: 35820889). 35820889
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) (PMID: 36093526). 36093526
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, neoadjuvant Alecensa (alectinib) treatment resulted in a complete pathological response in one patient with lung adenocarcinoma harboring EML4-ALK after 6 weeks and a major pathological response in another patient after 12 weeks of treatment, allowing for surgical resection in both (PMID: 36075183). 36075183
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in clinical symptom improvement and a partial response lasting at least 9 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e18) (PMID: 34763318). 34763318
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (PMID: 36324562). 36324562
EML4 - ALK large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in stable disease with early progression after 3 months in a patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20) (PMID: 36207130). 36207130
EML4 - ALK large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, second-line Alecensa (alectinib) treatment resulted in a partial response lasting 10 months in a patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20) (PMID: 36207130). 36207130
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a response lasting 19 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e19) (PMID: 29981924). 29981924
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a response lasting 24 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e19) who previously progressed on Xalkori (crizotinib) (PMID: 29981924). 29981924
EML4 - ALK mucosal melanoma sensitive ALK Inhibitor Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) inhibited downstream signaling and decreased viability of a mucosal melanoma cell line expressing EML4-ALK in culture and inhibited tumor growth in a cell line xenograft model (PMID: 29054983). 29054983
EML4 - ALK mucosal melanoma sensitive ALK Inhibitor Ceritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Zykadia (ceritinib) decreased viability of a mucosal melanoma cell line harboring EML4-ALK in culture and inhibited tumor growth in a cell line xenograft model (PMID: 29054983). 29054983
EML4 - ALK mucosal melanoma sensitive ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) decreased viability of a mucosal melanoma cell line harboring EML4-ALK in culture (PMID: 29054983). 29054983
EML4 - ALK mucosal melanoma sensitive ALK Inhibitor ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 decreased viability of a mucosal melanoma cell line harboring EML4-ALK in culture (PMID: 29054983). 29054983
EML4 - ALK mucosal melanoma sensitive ALK Inhibitor Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) decreased viability of a mucosal melanoma cell line harboring EML4-ALK in culture (PMID: 29054983). 29054983
EML4 - ALK large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in clinical improvement with a partial response including dramatic shrinkage in all of the known lesions in a patient with large cell lung neuroendocrine cancer and brain metastasis harboring EML4-ALK (PMID: 35280726). 35280726
EML4 - ALK inflammatory myofibroblastic tumor predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a decrease or disappearance of metastatic lesions after 10 months in a patient with inflammatory myofibroblastic tumor harboring EML4-ALK (e6:e20), who remained on treatment with good clinical condition at 16 months (PMID: 35280868). 35280868
EML4 - ALK inflammatory myofibroblastic tumor predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in tumor shrinkage with response lasting at least 28 months in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK (PMID: 36035049). 36035049
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment in a pediatric patient with metastatic lung adenocarcinoma harboring EML4-ALK resulted in a very good partial response at 2 months with regression of enlarged lymph nodes, with a near-complete response after 18 months of treatment (PMID: 36640634). 36640634
EML4 - ALK duodenum adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response with 57% tumor reduction after 49 days in a patient with metastatic duodenum adenocarcinoma harboring EML4-ALK, who remained on treatment and progression-free at 6 months (PMID: 36713517). 36713517
EML4 - ALK pulmonary neuroendocrine tumor predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic neuroendocrine carcinoma of the lung harboring EML4-ALK demonstrated a favorable response to Alecensa (alectinib), despite the appearance of new brain and adrenal lesions that were resolved with radiotherapy, and remained on treatment for at least 60 months (PMID: 36690569). 36690569
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Ensartinib Case Reports/Case Series Actionable In a clinical case study, neoadjuvant Ensartinib (X-396) resulted in a major pathological response and decreased tumor size allowing for resection 5 months after treatment intitation in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 36730477). 36730477
EML4 - ALK large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response after 1 month of treatment in a patient with lung large cell neuroendocrine carcinoma harboring EML4-ALK (e13:e20), with response lasting at least 12 months (PMID: 36819595). 36819595
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response within three months, with a reduction in liver metastases, in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20) (PMID: 36864442). 36864442
EML4 - ALK Smarca4-deficient sarcoma of thorax predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response after 6 weeks and a complete remission after 9 months of therapy in a patient with SMARCA4-deficient undifferentiated tumor of the thorax harboring EML4-ALK (e13:e20) (PMID: 36969551). 36969551
EML4 - ALK salivary gland cancer predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in an ongoing complete response after 8 months of treatment, with complete resolution of metastatic liver lesions, in a patient with metastatic salivary ductal carcinoma harboring EML4-ALK (PMID: 37041305). 37041305
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Iruplinalkib Preclinical - Cell line xenograft Actionable In a preclinical study, Iruplinalkib (WX-0593) inhibited tumor growth in a non-small cell lung cancer cell line xenograft model harboring EML4-ALK (PMID: 37036582). 37036582
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited tumor growth in a non-small cell lung cancer cell line xenograft model harboring EML4-ALK (PMID: 37036582). 37036582
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) inhibited tumor growth in a non-small cell lung cancer cell line xenograft model harboring EML4-ALK (PMID: 37036582). 37036582
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Lorlatinib + PF-07284892 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PF-07284892 and Lorbrena (lorlatinib) inhibited Erk phosphorylation in non-small cell lung cancer cells harboring EML4-ALK that was resistant to Lorbrena (lorlatinib), and induced tumor regression in a cell line xenograft model (PMID: 37269335). 37269335
EML4 - ALK inflammatory myofibroblastic tumor predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a near-complete radiographic response after 3 months in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK (PMID: 37255276). 37255276
EML4 - ALK intrahepatic cholangiocarcinoma predicted - sensitive ALK Inhibitor Ensartinib Case Reports/Case Series Actionable In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response with tumor regression in a patient with metastatic intrahepatic cholangiocarcinoma harboring EML4-ALK (PMID: 37675235). 37675235
EML4 - ALK large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Alectinib + Zoledronic acid Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Alecensa (alectinib) and Zoledronic acid resulted in a partial response with progression-free survival ongoing at 21 months in a patient with metastatic large cell neuroendocrine carcinoma harboring EML4-ALK (e6:e20) (PMID: 38023218). 38023218
EML4 - ALK large cell neuroendocrine carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response after 2 months of treatment in a patient with metastatic large cell neuroendocrine carcinoma harboring EML4-ALK (e20:e20), with response ongoing at 32 months (PMID: 38023218). 38023218
EML4 - ALK lung adenocarcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a radiological response after 8 weeks with a 50% decrease in tumor size in a pregnant patient with metastatic lung adenocarcinoma harboring EML4-ALK, and normal fetal development was observed (PMID: 38057186). 38057186
EML4 - ALK pulmonary neuroendocrine tumor predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in significant response in the lung and brain lesions in 2 patients with metastatic pulmonary atypical carcinoid tumor harboring EML4-ALK (e6:e20 or e13:e20), with progression-free survival of 6 and 9 months (PMID: 35832448). 35832448
EML4 - ALK lung adenocarcinoma sensitive ALK Inhibitor Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a complete response with a reduction in the brain metastases in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 38158887). 38158887
EML4 - ALK osteosarcoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in stable disease lasting at least 400 days in a patient with metastatic osteosarcoma harboring EML4-ALK (PMID: 38096470). 38096470
EML4 - ALK osteosarcoma predicted - sensitive ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease for nearly 60 weeks in a patient with metastatic osteosarcoma harboring EML4-ALK, who previously progressed on Alecensa (alectinib) treatment (PMID: 38096470). 38096470
EML4 - ALK renal cell carcinoma predicted - sensitive ALK Inhibitor Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a significant response in the brain and lung metastases in a patient with renal cell carcinoma harboring EML4-ALK (PMID: 29079636). 29079636
EML4 - ALK thyroid gland medullary carcinoma predicted - sensitive ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a decrease in the lung, liver, and bone lesions in a patient with metastatic medullary thyroid carcinoma harboring EML4-ALK (e13:e20) that was treated on a Phase I clinical trial (PMID: 26295973; NCT01121588). 26295973
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Afatinib + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Gilotrif (afatinib) and Xalkori (crizotinib) increased inhibition of downstream signaling, viability, and residual colony formation in a non-small cell lung cancer cell line harboring EML4-ALK compared to Xalkori (crizotinib) treatment alone in culture (PMID: 37748191). 37748191
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor Afatinib + Alectinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Gilotrif (afatinib) and Alecensa (alectinib) increased inhibition of downstream signaling, viability, and residual colony formation in a non-small cell lung cancer cell line harboring EML4-ALK compared to Alecensa (alectinib) treatment alone in culture (PMID: 37748191). 37748191