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Ref Type
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.
URL
Abstract Text

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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 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, Nov 2023). Y
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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
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