EML4 - ALK: Gene Variant Detail - Cancer Knowledgebase (CKB)

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Showing 1 to 131 of 131 entries

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK	lung non-small cell carcinoma	sensitive	Ensartinib	Phase II	Actionable	In a Phase II trial, Ensacove (ensartinib) 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 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	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	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	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	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	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	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	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	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	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	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	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	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 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	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	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	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 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	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 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 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	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	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	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	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	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	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	lung adenocarcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, neoadjuvant Ensacove (ensartinib) 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	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	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	intrahepatic cholangiocarcinoma	predicted - sensitive	Ensartinib	Case Reports/Case Series	Actionable	In a clinical case study, Ensacove (ensartinib) 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	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	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	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	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	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	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	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	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 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	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	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	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	malignant pleural mesothelioma	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 malignant pleural mesothelioma harboring EML4-ALK (e6:e20) (PMID: 39534944).	39534944
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	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 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	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 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	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 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 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	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 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	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	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	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	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 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 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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	Advanced Solid Tumor	sensitive	Ensartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ensacove (ensartinib) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191).	30002191
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	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	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	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	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	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	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	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	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	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	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	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	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	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	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 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	Advanced Solid Tumor	sensitive	Deulorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, Deulorlatinib (TGRX-326) inhibited viability of cells expressing EML4-ALK in culture (PMID: 39551469).	39551469
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 Ensacove (ensartinib) (PMID: 21613408).	21613408
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

Showing 1 to 131 of 131 entries

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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

EML4 - ALK - Gene Variant Detail

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