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|Authors||Wang HY, Ho CC, Shih JY|
|Title||Multiple Acquired Resistance Mutations of the ALK Tyrosine Kinase Domain after Sequential Use of ALK Inhibitors.|
|Journal||Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|ALK||D1203N||missense||unknown||ALK D1203N lies within the protein kinase domain of the Alk protein (UniProt.org). D1203N has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 35123209, PMID: 27432227, PMID: 28434515), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2023).||Y|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|EML4 - ALK ALK F1174L ALK D1203N ALK G1269A||lung adenocarcinoma||predicted - resistant||Ceritinib||Case Reports/Case Series||Actionable||In a clinical case study, ALK D1203N were identified as a newly acquired mutation in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Zykadia (ceritinib) treatment, in addition to the EML4-ALK, ALK F1174L, and ALK G1269A acquired after disease progression on Xalkori (crizotinib) and Belizatinib (TSR-011) sequentially (PMID: 28434515).||28434515|
|EML4 - ALK ALK L1196M||lung adenocarcinoma||predicted - resistant||Crizotinib||Case Reports/Case Series||Actionable||In a clinical case study, EML4-ALK and ALK L1196M were identified as acquired mutations in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Xalkori (crizotinib) treatment (PMID: 28434515).||28434515|
|EML4 - ALK ALK F1174L ALK G1269A||lung adenocarcinoma||predicted - resistant||Belizatinib||Case Reports/Case Series||Actionable||In a clinical case study, ALK F1174L and ALK G1269A were identified as newly acquired mutations in the pleural effusion from a patient with lung adenocarcinoma harboring an acquired EML4-ALK after his disease progressed on Belizatinib (TSR-011) treatment (PMID: 28434515).||28434515|