ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 681 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multi-Center Open-Label Phase 1/2 Study of BGB324 in Combination With Erlotinib in Patients With Stage IIIb or Stage IV Non-Small Cell Lung Cancer
A Phase Ib/II Multicenter Open-label Study of BGB324 as a Single Agent and in Combination With Cytarabine or Decitabine in Patients With Acute Myeloid Leukemia or as a Single Agent in Patients With Myelodysplastic Syndrome
Who cites it
681 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,115 citations in OpenAlex.
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- PD-L1 Activity Is Associated with Partial EMT and Metabolic Reprogramming in Carcinomas.Current oncology (Toronto, Ont.) · 2022Pooled it
- Phase I/II Study of AXL-Specific Antibody-Drug Conjugate Enapotamab Vedotin in Patients with Advanced Solid Tumors.Cancer research communications · 2025Trial
- Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.Nature communications · 2023Trial
- Acquired Genomic Alterations on First-Line Chemotherapy With Cetuximab in Advanced Colorectal Cancer: Circulating Tumor DNA Analysis of the CALGB/SWOG-80405 Trial (Alliance).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity.Cancer cell · 2022Trial
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- Targeting the EpCAM-AXL axis to overcome drug resistance in lung cancer.Molecular oncology · 2026Article
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Digital Twins for Targeted Therapy in Head and Neck Cancer: From Molecular Stratification to Resistance-Aware Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- ZNF217 promotes receptor tyrosine kinase plasticity and AXL-ERK dependency in ovarian cancer.bioRxiv : the preprint server for biology · 2026Article
- Cadherin-26 Promotes Airway Remodeling via Stabilizing Epithelial Expression of the Epidermal Growth Factor Receptor in Asthma.Allergy, asthma & immunology research · 2026Article
- Current therapeutic interventions to target cancer stem cells for metastasis.International journal of clinical oncology · 2026Review
- PROFET predicts continuous gene expression dynamics from scRNA-seq data to elucidate heterogeneity of cancer treatment responses.Cell systems · 2026Article
- Adaptive epithelial-mesenchymal bi-directional transition: A key invasive plasticity for tumor metastasis.iScience · 2026Review
- Combination AURKA and WEE1 Inhibition Exhibits Efficacy in EGFR or Pan-ERBB Inhibitor-Resistant Head and Neck Squamous Cell Carcinoma.Cancer research communications · 2026Article
- YAP1 Defines an Emergent, Plastic Population of Relapsed SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Palladium-catalyzed Suzuki-Miyaura and Buchwald-Hartwig cross-coupling reactions towards the synthesis of pharmacologically potent pyrimidine-based molecules.Molecular diversity · 2026Review
- SETDB1-mediated repression of RhoB promotes EMT and metastatic progression in prostate cancer.Oncogene · 2026Article
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
621 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
34 authors at 5 institutions in 1 country.
Funding
Abstract
purposeEpithelial-mesenchymal transition (EMT) has been associated with metastatic spread and EGF receptor (EGFR) inhibitor resistance. We developed and validated a robust 76-gene EMT signature using gene expression profiles from four platforms using non-small cell lung carcinoma (NSCLC) cell lines and patients treated in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) study. EXPERIMENTAL
designWe conducted an integrated gene expression, proteomic, and drug response analysis using cell lines and tumors from patients with NSCLC. A 76-gene EMT signature was developed and validated using gene expression profiles from four microarray platforms of NSCLC cell lines and patients treated in the BATTLE study, and potential therapeutic targets associated with EMT were identified.
resultsCompared with epithelial cells, mesenchymal cells showed significantly greater resistance to EGFR and PI3K/Akt pathway inhibitors, independent of EGFR mutation status, but more sensitivity to certain chemotherapies. Mesenchymal cells also expressed increased levels of the receptor tyrosine kinase Axl and showed a trend toward greater sensitivity to the Axl inhibitor SGI-7079, whereas the combination of SGI-7079 with erlotinib reversed erlotinib resistance in mesenchymal lines expressing Axl and in a xenograft model of mesenchymal NSCLC. In patients with NSCLC, the EMT signature predicted 8-week disease control in patients receiving erlotinib but not other therapies.
conclusionWe have developed a robust EMT signature that predicts resistance to EGFR and PI3K/Akt inhibitors, highlights different patterns of drug responsiveness for epithelial and mesenchymal cells, and identifies Axl as a potential therapeutic target for overcoming EGFR inhibitor resistance associated with the mesenchymal phenotype.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.