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    BIOMARKER:

    ALK fusion + EML4-ALK variant 3 + TP53 mutation

    i
    Other names: NBLST3, CD246, Anaplastic Lymphoma Kinase, Anaplastic Lymphoma Kinase (Ki-1), CD246 Antigen, Mutant Anaplastic Lymphoma Kinase, ALK, ALK Receptor Tyrosine Kinase, Anaplastic Lymphoma Receptor Tyrosine Kinase, ALK Tyrosine Kinase Receptor, EML4, EMAP Like 4, Restrictedly Overexpressed Proliferation-Associated Protein, Echinoderm Microtubule-Associated Protein-Like 4, Echinoderm Microtubule Associated Protein Like 4, Ropp 120, C2orf2, EMAP-4, EMAPL4, ROPP120, ELP120, TP53, Tumor Protein P53, Cellular Tumor Antigen P53, Phosphoprotein P53, Tumor Protein P53, Antigen NY-CO-13, Transformation-Related Protein 53, Mutant Tumor Protein 53, P53 Tumor Suppressor, Tumor Suppressor P53, Tumor Protein 53, BMFS5, TRP53, BCC7, LFS1
    Entrez ID:
    238; 7157; 27436
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    1m
    Small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3 and TP53 mutations after distinct responses to tyrosine kinase inhibitors: A case report. (PubMed, Heliyon)
    After the initial treatment with ensartinib, the patient experienced intracranial disease progression...Subsequent thoracic RT resulted in a partial response of the primary tumor; however, new brain and bone metastases were detected, prompting a switch to lorlatinib...Despite pembrolizumab treatment, the patient's condition deteriorated, and she passed away...Our findings revealed heterogeneity in ALK mutations and responses to ALK-TKIs, necessitating the close monitoring of genetic subtypes and associated mutations for tailored treatment strategies. Maintaining a heightened awareness of potential intestinal metastasis and vigilance in monitoring intestinal symptoms and abdominal metastases are pivotal for managing advanced lung adenocarcinoma.
    Journal • PD(L)-1 Biomarker
    |
    PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4)
    |
    TP53 mutation • ALK fusion • ALK mutation • EML4-ALK variant 3 + TP53 mutation • ALK fusion + EML4-ALK variant 3 + TP53 mutation
    |
    Keytruda (pembrolizumab) • Lorbrena (lorlatinib) • Ensacove (ensartinib)
    over1year
    Impact of EML4-ALK fusion variant and co-occurring TP53 mutation on treatment duration of first-line next-generation ALK TKIs in ALK fusion+ NSCLC. (ASCO 2023)
    Pts with advanced/metastatic NSCLC who were ALK+ in circulating tumor DNA by Guardant360 (G360) liquid biopsy test from Jan 1, 2018, to Dec 31, 2021, and received 1L monotherapy with a next-generation ALK TKI (alectinib, brigatinib, ceritinib, lorlatinib) were identified in the Guardant INFORM clinical-genomics database. Among pts with NSCLC and ALK fusion, co-occurrence of EML4-ALK V3 and TP53 mutation is common and associated with poor prognosis and high risk of early discontinuation of 1L treatment with a next-generation ALK TKI, most likely due to disease progression. Additional novel or combination therapies are warranted for this subpopulation. >a 117 pts had data for both TP53 and EML4-ALK V1 or V3.
    Clinical
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4)
    |
    TP53 mutation • ALK positive • EML4-ALK fusion • ALK fusion • ALK mutation • EML4-ALK variant 3 + TP53 mutation • ALK fusion + EML4-ALK variant 3 + TP53 mutation
    |
    Guardant360® CDx
    |
    Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)