Abstract
Glioblastoma (GBM) is a deadly brain cancer, and all attempts to control it have failed so far. However, the future looks bright, as we now know the molecular landscape of GBM through the work of The Cancer Genome Atlas (TCGA) program. GBMs exhibit significant inter- and intratumoral heterogeneity, and to control this type of tumor, a personalized approach is required. One target, whose gene is amplified and mutated in a large number of GBMs, is the epidermal growth factor receptor (EGFR). But all attempts to target it have been unsuccessful. We attribute the reason for this failure to the molecular heterogeneity of EGFR in GBM, as well as to the poor brain penetration of previously tested EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs). In this review, we discuss the molecular heterogeneity of EGFR and provide rational preclinical and clinical guidelines for testing AZD9291, a third generation, irreversible EGFR-TKI with both a high affinity for EGFRvIII and excellent brain penetration.
Keywords: Glioblastoma, EGFR, heterogeneity, targeted, therapies, TCGA.
Current Cancer Drug Targets
Title:A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma
Volume: 17 Issue: 3
Author(s): Madan M. Kwatra
Affiliation:
Keywords: Glioblastoma, EGFR, heterogeneity, targeted, therapies, TCGA.
Abstract: Glioblastoma (GBM) is a deadly brain cancer, and all attempts to control it have failed so far. However, the future looks bright, as we now know the molecular landscape of GBM through the work of The Cancer Genome Atlas (TCGA) program. GBMs exhibit significant inter- and intratumoral heterogeneity, and to control this type of tumor, a personalized approach is required. One target, whose gene is amplified and mutated in a large number of GBMs, is the epidermal growth factor receptor (EGFR). But all attempts to target it have been unsuccessful. We attribute the reason for this failure to the molecular heterogeneity of EGFR in GBM, as well as to the poor brain penetration of previously tested EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs). In this review, we discuss the molecular heterogeneity of EGFR and provide rational preclinical and clinical guidelines for testing AZD9291, a third generation, irreversible EGFR-TKI with both a high affinity for EGFRvIII and excellent brain penetration.
Export Options
About this article
Cite this article as:
Kwatra M. Madan, A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma, Current Cancer Drug Targets 2017; 17 (3) . https://dx.doi.org/10.2174/1568009616666161227091522
DOI https://dx.doi.org/10.2174/1568009616666161227091522 |
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
-
Regulation of the Urokinase Receptor (uPAR) by LDL Receptor-related Protein-1 (LRP1)
Current Pharmaceutical Design Raman Spectroscopy and Imaging: Promising Optical Diagnostic Tools in Pediatrics
Current Medicinal Chemistry Stimuli-Responsive Nanocarriers for Drug Delivery to the Central Nervous System
Current Nanoscience Inhibitors of the TGF-β Superfamily and their Clinical Applications
Mini-Reviews in Medicinal Chemistry Editorial [Hot topic: Targeting Nitric Oxide for Tumor Therapy (Executive Editor: Antonio Contestabile)]
Current Pharmaceutical Design Phosphoinositide 3-Kinases and Leukocyte Migration
Current Immunology Reviews (Discontinued) Distinctive Cellular Roles for Novel Protein Kinase C Isoenzymes
Current Pharmaceutical Design Molecular Mechanisms Regulating mRNA Stability: Physiological and Pathological Significance
Current Genomics Recent Advances in Radiation Therapy of Cancer Cells: A Step towards an Experimental and Systems Biology Framework
Current Radiopharmaceuticals Mechano-Regulation of Alternative Splicing
Current Genomics Isoliquiritigenin (ISL) and its Formulations: Potential Antitumor Agents
Current Medicinal Chemistry The Past, Current Studies and Future of Organometallic <sup>99m</sup>Tc(CO)3 Labeled Peptides and Proteins
Current Pharmaceutical Design Gene Therapy for Brain Cancer: Combination Therapies Provide Enhanced Efficacy and Safety
Current Gene Therapy Regulation of the PI3K-Akt Network: Current Status and a Promise for the Treatment of Human Diseases
Current Signal Transduction Therapy Oncolytic Viruses for Induction of Anti-Tumor Immunity
Current Pharmaceutical Biotechnology Recent Advances of Aminopyrimidines in Multicomponent Reactions
Current Organic Chemistry Editorial (Thematic Issue: PET/CT in External Beam Radiation Therapy Dose Planning)
Current Radiopharmaceuticals Ginsenoside Rh2 Inhibits Migration of Lung Cancer Cells under Hypoxia via mir-491
Anti-Cancer Agents in Medicinal Chemistry An Appraisal of Current Pharmacological Perspectives of Sesamol: A Review
Mini-Reviews in Medicinal Chemistry Novel Strategies in Cancer Therapeutics: Targeting Enzymes Involved in Cell Cycle Regulation and Cellular Proliferation
Current Cancer Drug Targets