^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    BIOMARKER:

    EML4-ALK rearrangement

    i
    Other names: 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, 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
    Entrez ID:
    238; 27436
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    5ms
    A Real-World Molecular Epidemiological Study of Non-Small-Cell Lung Cancer (NSCLC) Patients from Western India. (PubMed, South Asian J Cancer)
    Conclusion  Oncogenic driver mutations are present in Indian NSCLC patients. Molecular testing should be performed for all patients of advanced NSCLC to identify those that can benefit from newer generation of targeted or immunotherapies.
    Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4)
    |
    KRAS mutation • EGFR mutation • ALK rearrangement • EML4-ALK fusion • ALK fusion • ROS1 positive • EML4-ALK rearrangement
    6ms
    Preliminary Results of Phase 2 Open Label Study of Lorlatinib Monotherapy in Relapsed/Refractory ALK + Lymphomas Previously Treated with Other Tyrosine Kinase Inhibitors (ASH 2023)
    Median prior therapy lines was 3 (range 2-5); all pts previously received Crizotinib, two pts received also Alectinib and 1 Ceritinib as TKI treatment. Lorlatinib represents a safe and effective salvage therapy for ALK+ Lymphoma patients failing first line TKI treatment. The obtainment of CR at M1 seems to represent a pivotal prognostic factor. Lorlatinib also offers a promising bridging regimen to salvage ASCT especially for ALK+ BCL patients, with high response rates and no additional toxicities, .
    Clinical • P2 data
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4)
    |
    ALK rearrangement • ALK fusion • ALK translocation • EML4-ALK rearrangement
    |
    Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib)
    10ms
    Discovery of potent and effective inhibitors containing sulfoxide structures targeting EML4-ALK rearrangement and EGFR mutant non-small cell lung cancer. (PubMed, Bioorg Chem)
    Notably, (+)-8l significantly suppressed tumor growth in the H1975 cell-inoculated xenograft model (20 mg/kg/d, TGI: 96.11%), PC9 cell-inoculated xenograft model (20 mg/kg/d, TGI: 96.61%) and EML4 ALK-Baf3 cell-inoculated xenograft model (30 mg/kg/d, TGI: 80.86%). These results highlight the differentiated potential of (+)-8l to inhibit ALK rearrangement and EGFR mutation in NSCLC.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    EGFR mutation • ALK rearrangement • EML4-ALK rearrangement • EGFR H1975 • EGFR rearrangement
    10ms
    Pathological complete response to long-course neoadjuvant alectinib in lung adenocarcinoma with EML4-ALK rearrangement: report of two cases and systematic review of case reports. (PubMed, Front Oncol)
    However, large clinical trials must be conducted in the future to determine the treatment course and efficacy of the neoadjuvant alectinib modality. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022376804.
    Review
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK positive • ALK rearrangement • EML4-ALK rearrangement
    |
    Alecensa (alectinib)
    1year
    Lung cancer presenting with central nervous system metastasis: Clinicopathological and molecular analysis of 171 cases. (PubMed, Ann Diagn Pathol)
    This study highlights a highly heterogeneous molecular background in lung cancer presenting with CNS metastases. These findings highlight the need for individualized tumor testing strategies looking for potential therapeutic targets for this aggressive disease.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NKX2-1 (NK2 Homeobox 1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    KRAS mutation • EGFR mutation • HER-2 expression • ALK rearrangement • RET rearrangement • EML4-ALK rearrangement
    1year
    Tumor agnostic comparison of immunohistochemistry and next-generation sequencing in detecting ALK fusions and assessment of ALK tyrosine kinase inhibitor efficacy (ESMO-TAT 2023)
    The most frequent ALK TKIs were alectinib (n= 87, 58%) and crizotinib (n= 56, 38%). Conclusions In a population including multiple tumor types, NGS and IHC were highly concordant in ALK fusion detection. ALK TKI benefit may be observed in cases with discordant testing, in which only one assay detects a putative ALK fusion.
    Clinical • Next-generation sequencing • Pan tumor
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • TRIM24 (Tripartite Motif Containing 24)
    |
    ALK positive • ALK rearrangement • EML4-ALK fusion • ALK fusion • EML4-ALK rearrangement
    |
    MSK-IMPACT
    |
    Xalkori (crizotinib) • Alecensa (alectinib)
    over1year
    Endobronchial Metastases in Lung Cancer Harboring EML4-ALK Rearrangement. (PubMed, Intern Med)
    No abstract available
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK rearrangement • EML4-ALK rearrangement
    over1year
    Potential Therapeutic Strategy for EGFR-Mutant Lung Cancer With Concomitant EML4-ALK Rearrangement-Combination of EGFR Tyrosine Kinase Inhibitors and ALK Inhibitors. (PubMed, JTO Clin Res Rep)
    PC-9_v3a-gef and PC-9_v3b-gef cells were resistant to gefitinib and ALK inhibitors alone, but ALK inhibitors enhanced gefitinib-induced cytotoxicity. Furthermore, combination treatment with osimertinib and ceritinib caused a decrease in liver tumor size of the patient with liver metastases. Our data suggest that combination treatment with EGFR and ALK inhibitors can be a therapeutic strategy for treating NSCLC with concomitant EGFR mutation and EML4-ALK rearrangement.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • EML4 (EMAP Like 4)
    |
    EGFR mutation • EGFR exon 19 deletion • EGFR expression • ALK rearrangement • ALK fusion • EML4-ALK variant 3 • EML4-ALK rearrangement • ALK V3a • ALK V3b • EML4-ALK variant 3a
    |
    Tagrisso (osimertinib) • gefitinib • Zykadia (ceritinib)
    over1year
    Real-world data on treatment outcome of ALK positive non-small cell lung cancer from an Indian multi-centric cancer registry (ESMO Asia 2022)
    Results In 1st line, ORR with ALKi was 63.6% [crizotinib: 60.7%, ceritinib: 70%, alectinib: 66.6%, p=0.508] and that with chemotherapy was 26.1%. Patients who received ALKi in second or later lines fared much better in comparison to chemotherapy. Use of ALKi in any lines of therapy resulted in significantly prolonged OS.
    Clinical • Real-world evidence
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK positive • ALK rearrangement • EML4-ALK rearrangement
    |
    Xalkori (crizotinib) • Alecensa (alectinib) • Zykadia (ceritinib)
    over1year
    Treatment of ALK positive metastatic adenocarcinoma lung - A case report of sequencing therapy. (ESMO Asia 2022)
    He was started on Alectinib 600mg twice daily with zoledronic acid from Aug 2017. Molecular testing and looking for ALK resistance mutation helps to choose Lorlatinib, the only sensitive TKI which targets (G1202R). This is an evolving precision based therapy, improves outcome in lung cancer.
    Clinical
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK positive • ALK rearrangement • ALK G1202R • EML4-ALK rearrangement • EML4-ALK G1202R
    |
    Alecensa (alectinib) • Lorbrena (lorlatinib) • zoledronic acid
    over1year
    Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors. (PubMed, J Cancer Res Clin Oncol)
    Patients with SMARCA4-deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.
    Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • ALK rearrangement • STK11 mutation • SMARCA4 mutation • EML4-ALK rearrangement
    |
    Xalkori (crizotinib)
    almost2years
    A Combination of Cytokine-Induced Killer Cells With PD-1 Blockade and ALK Inhibitor Showed Substantial Intrinsic Variability Across Non-Small Cell Lung Cancer Cell Lines. (PubMed, Front Oncol)
    Taken together, we could show that CIK cells in combination with crizotinib and nivolumab can enhance the anti-tumor immune response through FasL activation, leading to increased IFN-γ and granzyme B, but only in NCI-H2228 cells with EML4-ALK rearrangement. Therefore, we hypothesize that CIK therapy may be a potential alternative in NSCLC patients harboring EML4-ALK rearrangement, in addition, we support the idea that combination therapies offer significant potential when they are optimized on a patient-by-patient basis.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • IFNG (Interferon, gamma) • FASLG (Fas ligand) • NCAM1 (Neural cell adhesion molecule 1) • GZMB (Granzyme B) • FAS (Fas cell surface death receptor) • FOXP3 (Forkhead Box P3)
    |
    KRAS mutation • ALK rearrangement • ROS1 rearrangement • EML4-ALK rearrangement • IL2RA expression • FOXP3 expression
    |
    Opdivo (nivolumab) • Xalkori (crizotinib)
    almost3years
    Identification of an EML4-ALK rearrangement in an intrahepatic cholangiocarcinoma. (PubMed, Pathol Int)
    No abstract available
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK rearrangement • EML4-ALK rearrangement
    almost3years
    EML4-ALK positive lung adenocarcinoma with skeletal muscle metastasis in the right calf which was treatable with lorlatinib after resistance to treatment with alectinib. (PubMed, BMJ Case Rep)
    After starting treatment with lorlatinib, the gastrocnemius tumour diminished and has maintained a stable condition. Our case suggests that EML4-ALK positive lung adenocarcinoma is treatable with lorlatinib after resistance to treatment with alectinib.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK positive • ALK rearrangement • EML4-ALK rearrangement
    |
    Alecensa (alectinib) • Lorbrena (lorlatinib)
    3years
    BRAF V600E mutation as a novel mechanism of acquired resistance to ALK inhibition in ALK-rearranged lung adenocarcinoma: A case report. (PubMed, Medicine (Baltimore))
    We present a case of ALK-rearranged lung adenocarcinoma with acquired resistance to ALK inhibition, in which the BRAF V600E mutation is a novel resistance mechanism. This provides evidence that BRAF V600E mutation is one mechanism of ALK-TKI resistance.
    Clinical • Preclinical • Journal
    |
    BRAF (B-raf proto-oncogene) • EML4 (EMAP Like 4)
    |
    BRAF V600E • BRAF V600 • ALK rearrangement • EML4-ALK rearrangement • ALK I1171T • ALK I1171 • EML4-ALK I1171T
    |
    Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib)
    3years
    [VIRTUAL] ALK fusions can be clearly detected in extracellular vesicles from NSCLC cell lines: A become of hope for non-invasive ALK testing (AACR 2021)
    EML4-ALK fusions can be detected at the RNA levels and at the protein levels analyzing EVs derived from H3122 and H2228 cell lines. These results set the stage for the development of EV-based non-invasive ALK testing in NSCLC patients.
    Preclinical
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • CD9 (CD9 Molecule)
    |
    ALK rearrangement • EML4-ALK fusion • ALK fusion • EML4-ALK rearrangement • EML4-ALK variant 1
    |
    Oncomine™ Pan-Cancer Cell-Free Assay
    3years
    The effect of EML4-ALK break-apart ratio on crizotinib outcomes in non-small cell lung cancer harboring EML4-ALK rearrangement. (PubMed, J Cancer Res Clin Oncol)
    The intracranial progression during crizotinib treatment was significantly frequent in the pts with high ALK rearrangement (62.5-32.5%, P 0.039) In this study, we found that the high break-apart ratio can predict the extent of benefit from targeted therapy in ALK-positive NSCLC patients. Based on the results of this study, the percentage of the ALK rearrangement can be used to predict treatment outcome and to choose the optimal targeted agent in the treatment of metastatic ALK-positive NSCLC.
    Journal • Tumor Mutational Burden
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • EML4 (EMAP Like 4)
    |
    EGFR mutation • ALK positive • ALK rearrangement • EML4-ALK rearrangement
    |
    Xalkori (crizotinib)
    over3years
    The Prevalence of the EML4-ALK Fusion Gene in Cytology Specimens from Patients with Lung Adenocarcinoma. (PubMed, Pulm Med)
    The EML4-ALK rearrangement gene has high prevalence in selected lung adenocarcinoma and EGFR mutation-negative populations. ALK inhibitors in lung cancer can be openly considered for use in Indonesian patients to improve the outcome of this subset of patients.
    Clinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK positive • ALK rearrangement • EML4-ALK fusion • ALK fusion • EML4-ALK rearrangement
    over3years
    Different driver gene mutations in patients with synchronous multiple primary lung cancers: a case report. (PubMed, J Cardiothorac Surg)
    The present report highlights the clinical importance of molecular cancer biomarkers detection to guide management decisions in MPLC cases.
    Clinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    EGFR mutation • EGFR L858R • ALK rearrangement • EML4-ALK rearrangement
    over3years
    Prolonged survival without progression under crizotinib treatment. (PubMed, Cancer Treat Res Commun)
    The group disgnosed with EML4-ALK rearrangement, composes a little part of metastatic non-small cell lung cancer. In this case presented, I will focus on the start of crizotinib treatment and 53-month follow-up in remission in a patient, who has been operated twice and received cisplatin-based adjuvant chemotherapy twice, and relapsed for the second time as Stage-4.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK rearrangement • EML4-ALK rearrangement
    |
    cisplatin • Xalkori (crizotinib)