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Gene ALK
Variant L1152R
Impact List missense
Protein Effect unknown
Gene Variant Descriptions 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).
Associated Drug Resistance Y
Category Variants Paths

ALK mutant ALK L1152R

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Transcript NM_004304.5
gDNA chr2:g.29222404A>C
cDNA c.3455T>G
Protein p.L1152R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304 chr2:g.29222404A>C c.3455T>G p.L1152R RefSeq GRCh38/hg38
NM_004304.4 chr2:g.29222404A>C c.3455T>G p.L1152R RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29222404A>C c.3455T>G p.L1152R RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21791641). 21791641
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK L1152R in culture (PMID: 31446141). 31446141
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to Zykadia (ceritinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R lung non-small cell carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a brief response to Xalkori (crizotinib) treatment, but after 3 months showed tumor progression, and was found to harbor the secondary resistance mutation, ALK L1152R (PMID: 21791641). 21791641
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to ASP3026 in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of a cell line expressing EML4-ALK with ALK L1152R in culture (PMID: 31446141). 31446141
EML4 - ALK ALK L1152R lung cancer resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Zykadia (ceritinib) treatment in culture (PMID: 31925410). 31925410
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Iruplinalkib Preclinical - Cell culture Actionable In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive TQ-B3139 Preclinical - Cell culture Actionable In a preclinical study, TQ-B3139 (CT-117) inhibited proliferation of a cells expressing EML4-ALK with ALK L1152R in culture (PMID: 30210922). 30210922
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Ensartinib Preclinical - Cell culture Actionable In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK L1152R in culture (PMID: 31446141). 31446141
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
ALK L1152R ALK pos lung non-small cell carcinoma predicted - sensitive Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 25% (1/4) of patients with ALK-positive non-small cell lung cancer harboring ALK L1152R (n=3) or L1152V (n=1) (PMID: 31628085; NCT0321569). 31628085