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BIOMARKER:

EML4-ALK F1174C

i
Entrez ID:
11ms
ALK F1174S mutation impairs ALK kinase activity in EML4-ALK variant 1 and sensitizes EML4-ALK variant 3 to crizotinib. (PubMed, Front Oncol)
These findings highlight the complexity of drug selection when treating patients harboring resistance mutations and suggest that the F1174S mutation in EML4-ALK variant 1 is likely not a potent oncogenic driver. Additional oncogenic driver or other resistance mechanisms should be considered in the case of EML4-ALK variant 1 with F1174S mutation.
Journal
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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EML4-ALK fusion • ALK fusion • ALK mutation • EML4-ALK variant 3 • ALK F1174C • EML4-ALK variant 1 • EML4-ALK F1174C
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Xalkori (crizotinib) • Lorbrena (lorlatinib)
almost3years
Real-world circulating tumor DNA analysis depicts resistance mechanism and clonal evolution in ALK inhibitor-treated lung adenocarcinoma patients. (PubMed, ESMO Open)
Sequential postprogression plasma profiling revealed that increased lines of ALK inhibitors can accelerate the accumulation of ALK resistance mutations and may lead to treatment-refractory compound ALK mutations. The selection for optimal first-line TKI is very important to achieve a more efficacious long-term strategy and prevent the emergence of on-target resistance, which may provide guidance for clinical decision making.
Journal • Real-world evidence • Circulating tumor DNA
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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TP53 mutation • ALK positive • ALK fusion • ALK mutation • ALK G1202R • EML4-ALK L1196M • ALK F1174C • ALK L1196M • EML4-ALK G1202R • ALK D1203N • EML4-ALK F1174C
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib)
3years
A Novel Sequentially Evolved EML4-ALK Variant 3 G1202R/S1206Y Double Mutation In Cis Confers Resistance to Lorlatinib: A Brief Report and Literature Review. (PubMed, JTO Clin Res Rep)
Here, we report, for the first time, a novel, sequentially-evolved EML4-ALK variant 3 G1202R/S1206Y double mutation in cis detected in a patient with ALK-positive NSCLC after disease progression on sequential crizotinib, alectinib, and then lorlatinib. Three-dimensional computer modeling of this double mutation and other G1202R-based double mutations with lorlatinib (ALK G1202R/L1196M, ALK G1202R/F1174C, ALK G1202R/l1198F, ALK G1202R/G1269A) were provided to reveal how these double mutations may confer resistance to lorlatinib through diverse steric hindrances in the ALK kinase domain. In addition, we performed a comprehensive literature review on published acquired double or triple ALK mutations that are resistant to lorlatinib from both patient samples and in vitro mutagenesis experiments.
Review • Journal
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK positive • ALK mutation • EML4-ALK variant 3 • ALK G1202R • ALK G1269A • EML4-ALK L1196M • ALK F1174C • ALK L1196M • ALK S1206Y • EML4-ALK G1202R • EML4-ALK G1269A • EML4-ALK F1174C • EML4-ALK S1206Y
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib)