Abstract
The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, show dramatic effects against non-small cell lung cancer (NSCLC) with EGFR activating mutations. However, 25% – 30% of EGFR mutant lung cancer patients show intrinsic resistance, and the responders almost invariably acquire resistance to EGFR-TKIs within several years. Three mechanisms — second-site point mutation that substitutes methionine for threonine at position 790 (T790M) in EGFR, amplification of MET protooncogene, and overexpression of hepatocyte growth factor (HGF, a ligand of MET) — have been reported to contribute to resistance to EGFR-TKIs. These three factors were detected simultaneously in a population of patients with acquired resistance to EGFR-TKIs. Further investigations to develop optimal therapy based on accurate diagnosis of resistant mechanism are warranted to improve the prognosis of EGFR mutant lung cancer.
Keywords: Acquired resistance, EGFR mutation, gene amplification, lung cancer, tyrosine kinase inhibitor, HGF, gefitinib, erlotinib, intrinsic resistance, T790M mutation, Met amplification, fibroblasts, microenvironment, EGFR-TKI, ErbB3, PI3K, Akt
Current Signal Transduction Therapy
Title: HGF-MET in Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer
Volume: 6 Issue: 2
Author(s): Seiji Yano, Wei Wang, Qi Li, Tadaaki Yamada, Shinji Takeuchi, Kunio Matsumoto, Yasuhiko Nishioka and Saburo Sone
Affiliation:
Keywords: Acquired resistance, EGFR mutation, gene amplification, lung cancer, tyrosine kinase inhibitor, HGF, gefitinib, erlotinib, intrinsic resistance, T790M mutation, Met amplification, fibroblasts, microenvironment, EGFR-TKI, ErbB3, PI3K, Akt
Abstract: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, show dramatic effects against non-small cell lung cancer (NSCLC) with EGFR activating mutations. However, 25% – 30% of EGFR mutant lung cancer patients show intrinsic resistance, and the responders almost invariably acquire resistance to EGFR-TKIs within several years. Three mechanisms — second-site point mutation that substitutes methionine for threonine at position 790 (T790M) in EGFR, amplification of MET protooncogene, and overexpression of hepatocyte growth factor (HGF, a ligand of MET) — have been reported to contribute to resistance to EGFR-TKIs. These three factors were detected simultaneously in a population of patients with acquired resistance to EGFR-TKIs. Further investigations to develop optimal therapy based on accurate diagnosis of resistant mechanism are warranted to improve the prognosis of EGFR mutant lung cancer.
Export Options
About this article
Cite this article as:
Yano Seiji, Wang Wei, Li Qi, Yamada Tadaaki, Takeuchi Shinji, Matsumoto Kunio, Nishioka Yasuhiko and Sone Saburo, HGF-MET in Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer, Current Signal Transduction Therapy 2011; 6 (2) . https://dx.doi.org/10.2174/157436211795659928
DOI https://dx.doi.org/10.2174/157436211795659928 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Computational & Statistical Methodologies to Identify Biomarkers in Cancer
Current Cancer Therapy Reviews Sirtuin Inhibitors: An Overview from Medicinal Chemistry Perspective
Anti-Cancer Agents in Medicinal Chemistry The Genetic and Epigenetic Effects of 5-Azacytidine and its Major Breakdown Product Guanylurea
Epigenetic Diagnosis & Therapy (Discontinued) Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design Boron-Containing Compounds as Preventive and Chemotherapeutic Agents for Cancer
Anti-Cancer Agents in Medicinal Chemistry New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry The Imaging of Apoptosis with the Radiolabelled Annexin A5: A New Tool in Translational Research
Current Clinical Pharmacology Photocatalytic Activities, Kinetics and Adsorption Isotherm Studies of CeO2 Nanoparticles Synthesized via Low Temperature Combustion Method
Current Nanomaterials Nanoparticle Drug Delivery Systems: Recent Patents and Applications in Nanomedicine
Recent Patents on Nanomedicine The Role of Survivin for Radiation Oncology: Moving Beyond Apoptosis Inhibition
Current Medicinal Chemistry Review of Airway Illnesses by Kytococcus and Rothia and a Look at Inhalatory Vancomycin as a Treatment Support
Recent Patents on Anti-Infective Drug Discovery Identification of Novel Sesamol Dimers with Unusual Methylenedioxy Ring-Opening Skeleton and Evaluation of Their Antioxidant and Cytotoxic Activities
Current Organic Synthesis Rational Targeting of Peroxisome Proliferating Activated Receptor Subtypes
Current Medicinal Chemistry Molecular and Cellular Pathways as Treatment Targets for Biologic Therapies in Systemic Sclerosis
Current Medicinal Chemistry Functionalized Silver Nanoparticles for Sensing, Molecular Imaging and Therapeutic Applications
Current Nanomedicine A Constrained Probabilistic Matrix Decomposition Method for Predicting miRNA-disease Associations
Current Bioinformatics The Cooperative Effect between Polybasic Region (PBR) and Polysialyltransferase Domain (PSTD) within Tumor-Target Polysialyltranseferase ST8Sia II
Current Topics in Medicinal Chemistry Molecular Mechanisms of Liver Cancer
Anti-Cancer Agents in Medicinal Chemistry HLA Peptide-mediated Strategies for Modulation of Cellular and Humoral Immune Response in Transplantation
Current Pharmacogenomics Palifermin in theManagement of Mucositis in Hematological Malignancies: Current Evidences and Future Perspectives
Cardiovascular & Hematological Agents in Medicinal Chemistry