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PMID

(27091190)

Authors

Tchekmedyian N, Ali SM, Miller VA, Haura EB

Title

Acquired ALK L1152R Mutation Confers Resistance to Ceritinib and Predicts Response to Alectinib.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer	11	7	2016 07	e87-8	J Thorac Oncol

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Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
ALK	L1152R	missense	unknown	ALK L1152R lies within the protein kinase domain of the Alk protein (UniProt.org). L1152R has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 35123209, PMID: 36064579, PMID: 27091190), 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
ALK rearrange ALK L1152R	lung adenocarcinoma	predicted - resistant	Ceritinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, demonstrated a partial response following treatment with Zykadia (ceritinib), however, progressed after 4 months and was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule (PMID: 27091190).	27091190
ALK rearrange ALK L1152R	lung adenocarcinoma	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule following progression on Xalkori (crizotinib) and Zykadia (ceritinib), and was subsequently treated with Alecensa (alectinib), resulting in a partial response in all disease areas (PMID: 27091190).	27091190

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