Abstract
The epidermal growth factor (EGFR) 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, profoundly 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 antibody-dependent cell-mediated cytotoxicity. This article provides a 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 locally 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: 7 Issue: 7
Author(s): Igor Astsaturov, Roger B. Cohen and Paul Harari
Affiliation:
Keywords: EGFR, head and neck squamous cell cancer, cetuximab, monoclonal antibodies, radiation
Abstract: The epidermal growth factor (EGFR) 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, profoundly 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 antibody-dependent cell-mediated cytotoxicity. This article provides a 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 locally 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 Paul, EGFR-Targeting Monoclonal Antibodies in Head and Neck Cancer, Current Cancer Drug Targets 2007; 7 (7) . https://dx.doi.org/10.2174/156800907782418365
DOI https://dx.doi.org/10.2174/156800907782418365 |
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
-
Potential Interactions of Carotenoids with Other Bioactive Food Components in the Prevention of Chronic Diseases
Current Bioactive Compounds Editorial [ The Role of Epidermal Growth Factor Receptor (EGFR) Targeting Drugs in the Treatment of Cancer Guest Editor: Fortunato Ciardiello ]
Current Cancer Therapy Reviews EDITORIAL(Hot Topic Integrated Therapeutic Approaches in the Treatment of Human Cancer)
Anti-Cancer Agents in Medicinal Chemistry Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy
Current Drug Targets Transcriptional Regulation of mPGES1 in Cancer: An Alternative Approach to Drug Discovery?
Current Drug Targets Regulatory T Cells and Skin Tumors
Recent Patents on Inflammation & Allergy Drug Discovery Application of VEGF Gene Therapy in Two Basic Fields of Plastic- Reparative Surgery: Tissue Reconstruction with Flaps and Peripheral Nerve Surgery
Recent Patents on Regenerative Medicine Liposomes as Nanovaccine Delivery Systems
Current Topics in Medicinal Chemistry Mitochondria and Familial Predisposition to Breast Cancer
Current Genomics The Role of Androgen Under Normal and Pathological Conditions in Sebaceous Glands: The Possibility of Target Therapy
Current Molecular Pharmacology Phenolic Compounds in Prevention and Treatment of Skin Cancers: A Review
Current Medicinal Chemistry Helical Tomotherapy versus Conventional Technique for Post Mastectomy Left Sided Breast Cancer; Dosimetric Study
Reviews on Recent Clinical Trials Comparison of the Structure and Biological Activities of Wild-type and Mutant Liver-targeting Peptide Modified Recombinant Human Endostatin (rES-CSP) in Human Hepatocellular Carcinoma HepG2 Cells
Protein & Peptide Letters Patent Selections
Recent Patents on Biomarkers Cervical Cancer: Are There Potential New Targets? An Update on Preclinical and Clinical Results
Current Drug Targets Advances in Anticancer Antibody-Drug Conjugates and Immunotoxins
Recent Patents on Anti-Cancer Drug Discovery Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway
Anti-Cancer Agents in Medicinal Chemistry Nanoemulsions for Improved Efficacy of Phytotherapeutics- A Patent Perspective
Recent Patents on Nanotechnology Angiotensin-Converting Enzymes (ACE and ACE2) as Potential Targets for Malignant Epithelial Neoplasia: Review and Bioinformatics Analyses Focused in Oral Squamous Cell Carcinoma
Protein & Peptide Letters Control of Copper Status for Cancer Therapy
Current Cancer Drug Targets