Abstract
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. It is a devastating and intractable disease with a poor outcome. Aberrant receptor tyrosine kinase signaling is a key driver in gliomagenesis and resistance to treatment. EGFR gene amplification and mutations are an important genetic alteration in GBM resulting in increased expression of EGFR wild type (EGFRwt) as well as mutant oncogenic forms of the EGFR. EGFRvIII is the most common oncogenic mutant in GBM and is usually co-expressed with EGFRwt. EGFRvIII does not bind ligand and is constitutively active. Recent studies have also highlighted a key role for Met in gliomagenesis and the EGFR and Met may act in concert to promote the malignant phenotype. Met is transactivated by EGFRvIII and plays a key role in EGFRvIII-mediated resistance to targeted treatment. HGF, a Met ligand, is highly expressed in GBM. HGF and Met create an important autocrine signaling loop that promotes GBM invasion. In addition, HGF/Met is able to induce EGFR activation, leading to enhanced activation of oncogenic signaling in GBM. In this review, we discuss the evidence for EGFR and Met interaction in GBM and discuss the mechanisms and biological consequences of transactivation between the two kinases. Additionally, we discuss the therapeutic potential of targeting both EGFR and Met signaling for the treatment of GBM.
Keywords: EGFR, Met, glioma, glioblastoma, GBM, targeted treatment, synergistic, antagonistic. EGFR wild type, EGFRvIII, EGFR mutants.
Current Cancer Drug Targets
Title:The Role of EGFR-Met Interactions in the Pathogenesis of Glioblastoma and Resistance to Treatment
Volume: 17 Issue: 3
Author(s): Gao Guo, Ram N. Narayan, Lindsay Horton, Toral R. Patel and Amyn A. Habib
Affiliation:
Keywords: EGFR, Met, glioma, glioblastoma, GBM, targeted treatment, synergistic, antagonistic. EGFR wild type, EGFRvIII, EGFR mutants.
Abstract: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. It is a devastating and intractable disease with a poor outcome. Aberrant receptor tyrosine kinase signaling is a key driver in gliomagenesis and resistance to treatment. EGFR gene amplification and mutations are an important genetic alteration in GBM resulting in increased expression of EGFR wild type (EGFRwt) as well as mutant oncogenic forms of the EGFR. EGFRvIII is the most common oncogenic mutant in GBM and is usually co-expressed with EGFRwt. EGFRvIII does not bind ligand and is constitutively active. Recent studies have also highlighted a key role for Met in gliomagenesis and the EGFR and Met may act in concert to promote the malignant phenotype. Met is transactivated by EGFRvIII and plays a key role in EGFRvIII-mediated resistance to targeted treatment. HGF, a Met ligand, is highly expressed in GBM. HGF and Met create an important autocrine signaling loop that promotes GBM invasion. In addition, HGF/Met is able to induce EGFR activation, leading to enhanced activation of oncogenic signaling in GBM. In this review, we discuss the evidence for EGFR and Met interaction in GBM and discuss the mechanisms and biological consequences of transactivation between the two kinases. Additionally, we discuss the therapeutic potential of targeting both EGFR and Met signaling for the treatment of GBM.
Export Options
About this article
Cite this article as:
Guo Gao, Narayan N. Ram, Horton Lindsay, Patel R. Toral and Habib A. Amyn, The Role of EGFR-Met Interactions in the Pathogenesis of Glioblastoma and Resistance to Treatment, Current Cancer Drug Targets 2017; 17 (3) . https://dx.doi.org/10.2174/1568009616666161215162515
DOI https://dx.doi.org/10.2174/1568009616666161215162515 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- 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
Related Articles
-
Epigenetic and Disease Targets by Polyphenols
Current Pharmaceutical Design Regulation of Radiation-Induced Apoptosis by Early Growth Response-1 Gene in Solid Tumors
Current Cancer Drug Targets New Pharmacological Approaches to the Cholinergic System: An Overview on Muscarinic Receptor Ligands and Cholinesterase Inhibitors
Recent Patents on CNS Drug Discovery (Discontinued) Adenoviral Vector Immunity: Its Implications and Circumvention Strategies
Current Gene Therapy TRAIL-Based Therapeutic Approaches for the Treatment of Pediatric Malignancies
Current Medicinal Chemistry Alkaloids from Cyanobacteria with Diverse Powerful Bioactivities
Mini-Reviews in Medicinal Chemistry Multifaceted Role of Neuropilins in Cancer
Current Medicinal Chemistry Evaluation of Non-Coding RNAs as Potential Targets in Head and Neck Squamous Cell Carcinoma Cancer Stem Cells
Current Drug Targets Antitumor Effects of Celastrol and Semi-Synthetic Derivatives
Mini-Reviews in Organic Chemistry Natural Products Targeting Autophagy via the PI3K/Akt/mTOR Pathway as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Metabotropic Glutamate Receptors in the Trafficking of Ionotropic Glutamate and GABAA Receptors at Central Synapses
Current Neuropharmacology Cytotoxic, Apoptotic and DNA Synthesis Inhibitory Effects of Some Thiazole Derivatives
Letters in Drug Design & Discovery Targeted Therapy for Brain Tumours: Role of PARP Inhibitors
Current Cancer Drug Targets Vitamins for Cancer Prevention and Treatment: An Insight
Current Molecular Medicine Importance of Kier-Hall Topological Indices in the QSAR of Anticancer Drug Design
Current Computer-Aided Drug Design Antineoplastic Activity of Monocrotaline Against Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Lectins in Human Cancer: Both a Devil and an Angel?
Current Protein & Peptide Science Targeting p73 - a Potential Approach in Cancer Treatment
Current Pharmaceutical Design Protein Transduction Revisited: Novel Insights Into the Mechanism Underlying Intracellular Delivery of Proteins
Current Pharmaceutical Design Cellular Targets for Anticancer Strategies
Current Drug Targets