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| Gene | EML4 ALK |
| Variant | EML4 - ALK |
| Impact List | fusion |
| Protein Effect | gain of function |
| Gene Variant Descriptions | EML4-ALK results from the fusion of EML4 and ALK, resulting in constitutive kinase activity, transformation in cultured cells, and tumor formation in mouse models (PMID: 19064915, PMID: 17625570, PMID: 35138907). EML4-ALK fusions have been associated with non-small cell lung cancer (PMID: 26755435). |
| Associated Drug Resistance | |
| Category Variants Paths |
ALK mutant ALK act mut EML4 - ALK ALK mutant ALK rearrange ALK fusion EML4 - ALK EML4 mutant EML4 fusion EML4 - ALK |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 squamous cell carcinoma | predicted - sensitive | 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 non-small cell carcinoma | sensitive | 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 non-small cell carcinoma | sensitive | 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 adenocarcinoma | sensitive | 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 | lung adenocarcinoma | sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a progression-free survival of 3.2 months in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20) and inhibited growth of a patient-derived organoid cell line in culture (PMID: 38983150). | 38983150 |
| EML4 - ALK | lung adenocarcinoma | sensitive | 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 | large cell neuroendocrine carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a response in the primary tumor and brain metastases in a patient with large cell neuroendocrine carcinoma of the lung harboring EML4-ALK (e6:e20) (PMID: 39395329). | 39395329 |
| EML4 - ALK | Advanced Solid Tumor | sensitive | 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 | 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 | mucosal melanoma | sensitive | 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 | Advanced Solid Tumor | sensitive | 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 | colon adenocarcinoma | predicted - sensitive | 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 | colon adenocarcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the pulmonary and mediastinal lymph node metastases in a patient with colon adenocarcinoma harboring EML4-ALK (PMID: 38381603). | 38381603 |
| EML4 - ALK | sarcoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a Phase II trial, Alecensa (alectinib) treatment resulted in a partial response in a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20) (PMID: 39188081). | 39188081 |
| EML4 - ALK | lung cancer | predicted - sensitive | 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 | pancreatic cancer | predicted - sensitive | 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 | osteosarcoma | predicted - sensitive | 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 | lung squamous cell carcinoma | predicted - sensitive | 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 | lung non-small cell carcinoma | sensitive | 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 adenocarcinoma | predicted - sensitive | 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 | 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 adenocarcinoma | predicted - sensitive | 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 | lung adenocarcinoma | predicted - sensitive | 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 | lung adenocarcinoma | predicted - sensitive | 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 | lung adenocarcinoma | predicted - sensitive | 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 | 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 | renal cell carcinoma | predicted - sensitive | 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 | papillary renal cell carcinoma | predicted - sensitive | 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 | pulmonary neuroendocrine tumor | predicted - sensitive | 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 | pulmonary neuroendocrine tumor | predicted - sensitive | 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 | malignant pleural mesothelioma | predicted - sensitive | 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 | salivary gland cancer | predicted - sensitive | 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 | duodenum adenocarcinoma | predicted - sensitive | 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 | large cell neuroendocrine carcinoma | predicted - sensitive | 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 | large cell neuroendocrine carcinoma | predicted - sensitive | 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 | large cell neuroendocrine carcinoma | predicted - sensitive | 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 | large cell neuroendocrine carcinoma | predicted - sensitive | 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 | large cell neuroendocrine carcinoma | predicted - sensitive | 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 | inflammatory myofibroblastic tumor | predicted - sensitive | 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 | 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 | inflammatory myofibroblastic tumor | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the primary tumor and brain metastasis in a patient with inflammatory myofibroblastic tumor harboring EML4-ALK (PMID: 38213097). | 38213097 |
| EML4 - ALK | mucosal melanoma | sensitive | 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 | lung mucoepidermoid carcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment beginning at 33 weeks gestation in a pregnant patient with metastatic mucoepidermoid carcinoma harboring EML4-ALK resulted in a near complete response during the postpartum period, and did not result in fetal or developmental anomalies for at least the first 11 months post birth (PMID: 34543940). | 34543940 |
| EML4 - ALK | ovarian serous carcinoma | predicted - sensitive | 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 | Smarca4-deficient sarcoma of thorax | predicted - sensitive | 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 | Advanced Solid Tumor | sensitive | 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 | neuroendocrine tumor | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, first-line treatment with Xalkori (crizotinib) resulted in shrinkage of the lung and adrenal gland lesions in a patient with a neuroendocrine tumor, consistent with atypical carcinoid tumor, harboring EML4-ALK (PMID: 30154667). | 30154667 |
| EML4 - ALK | neuroblastoma | resistant | 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 | pancreatic cancer | predicted - sensitive | 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 squamous cell carcinoma | predicted - sensitive | 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 non-small cell carcinoma | sensitive | 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 | lung non-small cell carcinoma | sensitive | 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 | 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 adenocarcinoma | predicted - sensitive | 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 | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in a complete response and a progression-free survival of 35 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) (PMID: 38978737). | 38978737 |
| EML4 - ALK | lung adenocarcinoma | predicted - sensitive | 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 | 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 | lung adenocarcinoma | predicted - sensitive | 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 | medullary thyroid carcinoma | predicted - sensitive | 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 | clear cell renal cell carcinoma | sensitive | Crizotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) treatment inhibited tumor growth in a cell line xenograft model of clear cell renal cell carcinoma expressing EML4-ALK (PMID: 32020234). | 32020234 |
| EML4 - ALK | large cell neuroendocrine carcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in regression of all previously identified lesions in a patient with large cell neuroendocrine carcinoma harboring EML4-ALK (PMID: 30154667). | 30154667 |
| EML4 - ALK | large cell neuroendocrine carcinoma | predicted - sensitive | 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 | inflammatory myofibroblastic tumor | predicted - sensitive | 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 | inflammatory myofibroblastic tumor | predicted - sensitive | 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 | mucosal melanoma | sensitive | 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 | colorectal carcinoma | predicted - sensitive | 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 | Advanced Solid Tumor | sensitive | 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 | 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 | 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 | sensitive | 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 | lung non-small cell carcinoma | sensitive | 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 adenocarcinoma | predicted - sensitive | 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 | lung adenocarcinoma | predicted - sensitive | 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 | mucosal melanoma | sensitive | 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 | Advanced Solid Tumor | sensitive | 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 | neuroblastoma | sensitive | 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 | osteosarcoma | predicted - sensitive | 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 | lung non-small cell carcinoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase III trial (CROWN), Lorbrena (lorlatinib) therapy resulted in an objective response rate (ORR) of 81% (120/149, 15 complete and 105 partial responses) and a median progression-free survival (mPFS) that was not reached at 5-year follow-up in ALK-positive non-small cell lung cancer patients, with an ORR of 80%, 100%, and 83% and an mPFS of 64.3 mo, not reached, and 60.0 mo in patients with EML4-ALK variants 1 (n=20), 2 (n=7), and 3a/b (n=18), respectively (PMID: 38819031; NCT03052608). | 38819031 |
| EML4 - ALK | lung non-small cell carcinoma | sensitive | 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 | lung adenocarcinoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a progression-free survival of 1.9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20) and inhibited growth of a patient-derived organoid cell line in culture (PMID: 38983150). | 38983150 |
| EML4 - ALK | lung adenocarcinoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in an intracranial response, with improvement of the metastatic brain lesions, in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20), who previously progressed on Alunbrig (brigatinib) (PMID: 38924375). | 38924375 |
| EML4 - ALK | lung adenocarcinoma | sensitive | 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 mucoepidermoid carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic pulmonary mucoepidermoid carcinoma harboring EML4-ALK (e6:e20) (PMID: 39259069). | 39259069 |
| EML4 - ALK | lung mucoepidermoid carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with pulmonary mucoepidermoid carcinoma harboring EML4-ALK (e20:e20) (PMID: 39267825). | 39267825 |
| EML4 - ALK | colorectal carcinoma | predicted - sensitive | 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 | epithelioid inflammatory myofibroblastic sarcoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a pathological complete response in a patient with epithelioid inflammatory myofibroblastic sarcoma harboring EML4-ALK (e6:e20) (PMID: 39144623). | 39144623 |
| EML4 - ALK | Advanced Solid Tumor | sensitive | 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 | lung non-small cell carcinoma | sensitive | 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 | 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 | intrahepatic cholangiocarcinoma | predicted - sensitive | 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 | Advanced Solid Tumor | sensitive | 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 | lung non-small cell carcinoma | sensitive | 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 | mucosal melanoma | sensitive | 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 | Advanced Solid Tumor | sensitive | 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 | 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 | 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 | lung cancer | sensitive | 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 | sensitive | 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 | 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 | 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 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 | Advanced Solid Tumor | sensitive | 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 | 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 | lung non-small cell carcinoma | sensitive | 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 | 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 |
| EML4 - ALK | lung non-small cell carcinoma | predicted - sensitive | 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 | 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 | 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 | Advanced Solid Tumor | sensitive | 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 | 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 | breast cancer | predicted - sensitive | 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 | 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 | predicted - sensitive | 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 cancer | predicted - sensitive | 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 | lung non-small cell carcinoma | sensitive | 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 | lung non-small cell carcinoma | sensitive | 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 | 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 | 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 | lung non-small cell carcinoma | sensitive | NVL-655 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, NVL-655 inhibited growth of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK in culture and inhibited growth of a cell line xenograft model (PMID: 39269178). | 39269178 |
| EML4 - ALK | lung adenocarcinoma | sensitive | NVL-655 | Case Reports/Case Series | Actionable | In a Phase I trial (ALKOVE-1), NVL-655 treatment resulted in a complete response in the central nervous system metastases and an overall partial response with treatment ongoing for at least 9 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (PMID: 39269178; NCT05384626). | 39269178 |
| EML4 - ALK | Advanced Solid Tumor | predicted - sensitive | NVL-655 | Preclinical - Cell culture | Actionable | In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK in culture (PMID: 39269178). | 39269178 |
| EML4 - ALK | lung non-small cell carcinoma | sensitive | 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 | Advanced Solid Tumor | sensitive | 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 | 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 | Advanced Solid Tumor | sensitive | 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 | 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 | 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 | large cell neuroendocrine carcinoma | predicted - sensitive | 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 |