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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. | ||||||||||||
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Abstract Text |
Molecular Profile | Treatment Approach |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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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 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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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 |