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Ref Type

PMID

(28434515)

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	Vol	Issue	Date	Pages	Journal Short Title
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer	12	5	2017 05	e49-e51	J Thorac Oncol

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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, Aug 2024).	Y

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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 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
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

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