Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : firstname.lastname@example.org
|Ref Type||Journal Article|
|Authors||Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H|
|Title||EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors.|
|Journal||The New England journal of medicine|
|Date||2010 Oct 28|
|Abstract Text||The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.).|
|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||C1156Y||missense||unknown||ALK C1156Y lies within the protein kinase domain of the Alk protein (UniProt.org). C1156Y has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 21613408, PMID: 20979473, PMID: 27490033, PMID: 27045755), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).||Y|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|EML4 - ALK ALK C1156Y ALK L1196M||lung adenocarcinoma||predicted - resistant||Crizotinib||Case Reports/Case Series||Actionable||In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK treated on a clinical trial achieved a partial response when treated with Xalkori (crizotinib), however, after 5 months, the patient progressed and was found to harbor secondary resistance mutations, ALK C1156Y and ALK L1196M (PMID: 20979473; NCT00585195).||20979473|