Abstract
Approximately 475,000 cases of squamous cell carcinoma (SCCHN) of the head and neck occur worldwide. Whereas significant advances have been made in the treatment of early and locally advanced disease, the prognosis for recurrent and metastatic (R/M) disease remains poor. Compounds with demonstrated activity include cisplatin and carboplatin, antimicrotubular compounds such as taxanes and vinorelbine, and fluoropyrimidines. In refractory and metastatic disease, regimens combining platinum agents with taxanes or fluorouracil based agents produce a 30% response rate and a median overall survival of six to eight months. Newer three agent chemotherapy regimens have produced response rates in the range of 40-50%, without significant improvements in overall survival noted. Recently, a new class of medications targeting signal transduction pathways has come into focus in the treatment of various malignancies. In SCCHN, given the high prevalence of expression of the epidermal growth factor receptor (EGFR) and its role in promoting cellular growth and proliferation, molecules targeting the receptors intracellular kinase domain are a logical strategy. The agents gefitinib and erlotinib have yielded response rates in the 5-15% range when used as single agents. In addition, newer agents with broad activity against the EGFR and other related erbB receptor family members are being developed in clinical trials. Strategies to enhance the activity of EGFR tyrosine kinase inhibitors (TKIs) in treating SCCHN are being investigated, as well as strategies to select individuals with tumors more likely to respond to these drugs. This article reviews the advances that have made in treating refractory and metastatic disease, with particular focus on the challenges that are faced in successfully translating EGFR inhibition as a paradigm of tumor treatment in SCCHN.
Keywords: Head and neck cancer, epidermal growth factor receptor, protein kinase inhibitors, quinazolines, chemotherapy, metastases
Current Cancer Drug Targets
Title: Treatment of Squamous Cell Carcinoma of the Head and Neck in the Metastatic and Refractory Settings: Advances in Chemotherapy and the Emergence of Small Molecule Epidermal Growth Factor Receptor Kinase Inhibitors
Volume: 7 Issue: 7
Author(s): Syed M. Ahmed and Ezra E.W. Cohen
Affiliation:
Keywords: Head and neck cancer, epidermal growth factor receptor, protein kinase inhibitors, quinazolines, chemotherapy, metastases
Abstract: Approximately 475,000 cases of squamous cell carcinoma (SCCHN) of the head and neck occur worldwide. Whereas significant advances have been made in the treatment of early and locally advanced disease, the prognosis for recurrent and metastatic (R/M) disease remains poor. Compounds with demonstrated activity include cisplatin and carboplatin, antimicrotubular compounds such as taxanes and vinorelbine, and fluoropyrimidines. In refractory and metastatic disease, regimens combining platinum agents with taxanes or fluorouracil based agents produce a 30% response rate and a median overall survival of six to eight months. Newer three agent chemotherapy regimens have produced response rates in the range of 40-50%, without significant improvements in overall survival noted. Recently, a new class of medications targeting signal transduction pathways has come into focus in the treatment of various malignancies. In SCCHN, given the high prevalence of expression of the epidermal growth factor receptor (EGFR) and its role in promoting cellular growth and proliferation, molecules targeting the receptors intracellular kinase domain are a logical strategy. The agents gefitinib and erlotinib have yielded response rates in the 5-15% range when used as single agents. In addition, newer agents with broad activity against the EGFR and other related erbB receptor family members are being developed in clinical trials. Strategies to enhance the activity of EGFR tyrosine kinase inhibitors (TKIs) in treating SCCHN are being investigated, as well as strategies to select individuals with tumors more likely to respond to these drugs. This article reviews the advances that have made in treating refractory and metastatic disease, with particular focus on the challenges that are faced in successfully translating EGFR inhibition as a paradigm of tumor treatment in SCCHN.
Export Options
About this article
Cite this article as:
Ahmed M. Syed and Cohen E.W. Ezra, Treatment of Squamous Cell Carcinoma of the Head and Neck in the Metastatic and Refractory Settings: Advances in Chemotherapy and the Emergence of Small Molecule Epidermal Growth Factor Receptor Kinase Inhibitors, Current Cancer Drug Targets 2007; 7 (7) . https://dx.doi.org/10.2174/156800907782418293
DOI https://dx.doi.org/10.2174/156800907782418293 |
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
-
Mitochondrial Drug Targets in Cell Death and Cancer
Current Pharmaceutical Design Versatile Applications of microRNA in Anti-Cancer Drug Discovery: From Therapeutics to Biomarkers
Current Drug Discovery Technologies Wnt / β-Catenin Signaling Pathway as Novel Cancer Drug Targets
Current Cancer Drug Targets Reversing Multidrug Resistance in Chemo-resistant Human Lung Adenocarcinoma (A549/DOX) Cells by Algerian Propolis Through Direct Inhibiting the P-gp Efflux-pump, G0/G1 Cell Cycle Arrest and Apoptosis Induction
Anti-Cancer Agents in Medicinal Chemistry Targeting CD4 to Disrupt Signaling Through Membrane Rafts: Towards a Raft-Based Therapeutics
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Realizing the Potential of Blueberry as Natural Inhibitor of Metastasis and Powerful Apoptosis Inducer: Tapping the Treasure Trove for Effective Regulation of Cell Signaling Pathways
Anti-Cancer Agents in Medicinal Chemistry Genetic and Modifying Factors that Determine the Risk of Brain Tumors
Central Nervous System Agents in Medicinal Chemistry Chemokines and Chemokine Receptors Blockers as New Drugs for the Treatment of Chronic Obstructive Pulmonary Disease
Current Medicinal Chemistry Invasive Aspergillosis in Children and Adolescents
Current Pharmaceutical Design Serotonin and Cancer: What Is the Link?
Current Molecular Medicine Epithelial-Mesenchymal Transitions and Cancer
Current Genomics Stable Loading and Delivery of Icaritin Using PEG-PCL Micelles for Effective Treatment of Oral Squamous Cell Carcinoma
Current Drug Delivery Applications and Limitations of Genetically Modified Mouse Models in Drug Discovery and Development
Current Drug Metabolism Targeted Regulation of PI3K/Akt/mTOR/NF-κB Signaling by Indole Compounds and their Derivatives: Mechanistic Details and Biological Implications for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Cytotoxic and Chemopreventive Effects of Gemin D Against Different Mutagens Using In Vitro and In Vivo Assays
Anti-Cancer Agents in Medicinal Chemistry The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment
Recent Patents on Anti-Cancer Drug Discovery Human Saliva Metabolome for Oral Lichen Planus Biomarker Identification
Recent Patents on Anti-Cancer Drug Discovery Biomarkers to Assess the Targeting of DNA Repair Pathways to Augment Tumor Response to Therapy
Current Molecular Medicine Bioactive Polyphenols from Healthy Diets and Forest Biomass
Current Nutrition & Food Science Empyema and Bronchopleural Fistula Following Lung Resection
Current Respiratory Medicine Reviews