Abstract
The epidermal growth factor (EGF) and its receptor were discovered nearly 40 years ago. Over the past decade interruption of this pathway has been exploited in the treatment of various solid tumors. Antibodies that interfere with ligand binding to and dimerization of the EGFR (and small molecules that inhibit the EGFR tyrosine kinase) are anti-proliferative, radiosensitizing, and synergistic with DNA-damaging cytotoxic agents. Proposed mechanisms of radio- and chemosensitization include enhanced apoptosis, interference with DNA repair and angiogenesis, receptor depletion from the cell surface and antibodydependent cell-mediated cytotoxicity. This article provides the reader with a comprehensive review of EGFR-targeting antibodies under development for the treatment of head and neck squamous cell cancer (HNSCC) and also summarizes relevant clinical data in this disease with small molecule EGFR inhibitors. One of the monoclonal antibodies, cetuximab, recently received full FDA approval for the treatment of patients with locoregionally advanced (with radiation) or metastatic HNSCC (as a single agent). Regulatory approval followed reporting of a large international study in which the addition of cetuximab to definitive radiation therapy in HNSCC resulted in statistically significant improvements in locoregional control and overall survival. Results of the pivotal trial, other clinical data supporting the regulatory approval, and a preview of the next generation of clinical trials are presented. Considerable work remains to be done, particularly to enhance our understanding of factors that may predict for favorable response to EGFR inhibitor therapy and to evaluate the impact of integrating anti-EGFR therapies into complex chemoradiation programs delivered with curative intent.
Keywords: EGFR, head and neck squamous cell cancer, cetuximab, monoclonal antibodies, radiation
Current Cancer Drug Targets
Title: EGFR-Targeting Monoclonal Antibodies in Head and Neck Cancer
Volume: 6 Issue: 8
Author(s): Igor Astsaturov, Roger B. Cohen and Paul M. Harari
Affiliation:
Keywords: EGFR, head and neck squamous cell cancer, cetuximab, monoclonal antibodies, radiation
Abstract: The epidermal growth factor (EGF) and its receptor were discovered nearly 40 years ago. Over the past decade interruption of this pathway has been exploited in the treatment of various solid tumors. Antibodies that interfere with ligand binding to and dimerization of the EGFR (and small molecules that inhibit the EGFR tyrosine kinase) are anti-proliferative, radiosensitizing, and synergistic with DNA-damaging cytotoxic agents. Proposed mechanisms of radio- and chemosensitization include enhanced apoptosis, interference with DNA repair and angiogenesis, receptor depletion from the cell surface and antibodydependent cell-mediated cytotoxicity. This article provides the reader with a comprehensive review of EGFR-targeting antibodies under development for the treatment of head and neck squamous cell cancer (HNSCC) and also summarizes relevant clinical data in this disease with small molecule EGFR inhibitors. One of the monoclonal antibodies, cetuximab, recently received full FDA approval for the treatment of patients with locoregionally advanced (with radiation) or metastatic HNSCC (as a single agent). Regulatory approval followed reporting of a large international study in which the addition of cetuximab to definitive radiation therapy in HNSCC resulted in statistically significant improvements in locoregional control and overall survival. Results of the pivotal trial, other clinical data supporting the regulatory approval, and a preview of the next generation of clinical trials are presented. Considerable work remains to be done, particularly to enhance our understanding of factors that may predict for favorable response to EGFR inhibitor therapy and to evaluate the impact of integrating anti-EGFR therapies into complex chemoradiation programs delivered with curative intent.
Export Options
About this article
Cite this article as:
Astsaturov Igor, Cohen B. Roger and Harari M. Paul, EGFR-Targeting Monoclonal Antibodies in Head and Neck Cancer, Current Cancer Drug Targets 2006; 6 (8) . https://dx.doi.org/10.2174/156800906779010191
DOI https://dx.doi.org/10.2174/156800906779010191 |
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
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
Unraveling the Tumor Microenvironment and Potential Therapeutic Targets: Insights from Single-Cell Sequencing and Spatial Transcriptomics
This special issue will focus on unraveling the complexities of the tumor microenvironment (TME) and identifying key biomarkers for potential therapeutic targets using advanced multi-omics techniques, such as single-cell sequencing and spatial transcriptomics. We seek original research and comprehensive reviews that investigate the heterogeneity and dynamics of the TME, emphasizing ...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
-
Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy
Current Gene Therapy Investigating the Molecular Basis of Drug Action and Response: Chemocentric Genomics and Proteomics
Current Drug Targets Stem Cell Genetic Therapy for Fanconi Anemia – A New Hope
Current Gene Therapy Impact of the Somatotrope Growth Hormone (GH)/Insulin-Like Growth Factor 1 (IGF-1) Axis Upon Thymus Function: Pharmacological Implications in Regeneration of Immune Functions
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Cancer-Targeting Multifunctionalized Gold Nanoparticles in Imaging and Therapy
Current Medicinal Chemistry KRAS Mutation Analysis Prior to EGFR-Directed Therapy for Metastatic Colorectal Cancer: A Review and Cost Analysis
Current Cancer Therapy Reviews RING-, HECT-, and RBR-type E3 Ubiquitin Ligases: Involvement in Human Cancer
Current Cancer Drug Targets Amino Acid Transporter-Targeted Radiotracers for Molecular Imaging in Oncology
Current Medicinal Chemistry Recent Advances of MEK Inhibitors and Their Clinical Progress
Current Topics in Medicinal Chemistry Therapy Stratifications and Novel Approach in Pursuit of Aids Related Kaposi’s Sarcoma Management- A paradigm for Non Invasiveness
Current Drug Delivery Development of NGR-Based Anti-Cancer Agents for Targeted Therapeutics and Imaging
Anti-Cancer Agents in Medicinal Chemistry Acid-extrusion from Tissue: The Interplay Between Membrane Transporters and pH Buffers
Current Pharmaceutical Design Growth Responses Following a Single Intra-Muscular hGH Plasmid Administration Compared to Daily Injections of hGH in Dwarf Mice
Current Gene Therapy Pollen Diversity, Antiradical and Antibacterial Activity and Phenolic Contents of some Polish Honeys
Current Nutrition & Food Science Antitumor Effects of Interferon-Alpha on Cell Growth and Metastasis in Human Nasopharyngeal Carcinoma
Current Cancer Drug Targets Antibodies as Crypts of Antiinfective and Antitumor Peptides
Current Medicinal Chemistry De Novo DNMTs and DNA Methylation: Novel Insights into Disease Pathogenesis and Therapy from Epigenomics
Current Pharmaceutical Design Nanoparticles: Properties and Applications in Cancer Immunotherapy
Current Pharmaceutical Design The Sam Domain of EphA2 Receptor and its Relevance to Cancer: A Novel Challenge for Drug Discovery?
Current Medicinal Chemistry Potential Applications of <i>Sarcopoterium Spinosum</i> as Medicinal Plants: Overview and Future Trends
Current Traditional Medicine