Abstract
Both the epidermal growth factor receptor (EGFR) and the insulin-like growth factor-1 receptor (IGF-1R) can contribute to tumor development and -progression through their effects on cell proliferation, inhibition of apoptosis, angiogenesis, anchorage-independent growth and tumor-associated inflammation. EGFR-targeting monoclonal antibodies and small molecule tyrosine kinase inhibitors are currently in clinical use for the treatment of several types of cancer. However, primary and acquired resistance to these agents often occurs and thereby limits the clinical efficacy of monospecific targeted therapy. Results from both in vitro and in vivo studies indicate that cross-talk between EGFR and IGF-1R can lead to acquired resistance against EGFR-targeted drugs. This review describes the interface between the EGFR and IGF-1R signaling networks and the implications of the extensive cross-talk between these two receptor systems for cancer therapy. EGFR and IGF-1R interact on multiple levels, either through a direct association between the two receptors, by mediating the availability of each others ligands, or indirectly, via common interaction partners such as G protein coupled receptors (GPCR) or downstream signaling molecules. This multi-layered cross-talk and its involvement in the induction of resistance to targeted therapies provide a clear rationale for dual targeting of EGFR and IGF-1R. We discuss several (potential) strategies to simultaneously inhibit EGFR and IGF-1R signaling as promising novel therapeutic approaches.
Keywords: Epidermal growth factor receptor, insulin-like growth factor-1 receptor, cross-talk, cancer therapy, dual targeting, resistance
Current Cancer Drug Targets
Title: Crosstalk Between Epidermal Growth Factor Receptor- and Insulin-Like Growth Factor-1 Receptor Signaling: Implications for Cancer Therapy
Volume: 9 Issue: 6
Author(s): J. van der Veeken, S. Oliveira, R. M. Schiffelers, G. Storm, P.M.P. van Bergen en Henegouwen and R. C. Roovers
Affiliation:
Keywords: Epidermal growth factor receptor, insulin-like growth factor-1 receptor, cross-talk, cancer therapy, dual targeting, resistance
Abstract: Both the epidermal growth factor receptor (EGFR) and the insulin-like growth factor-1 receptor (IGF-1R) can contribute to tumor development and -progression through their effects on cell proliferation, inhibition of apoptosis, angiogenesis, anchorage-independent growth and tumor-associated inflammation. EGFR-targeting monoclonal antibodies and small molecule tyrosine kinase inhibitors are currently in clinical use for the treatment of several types of cancer. However, primary and acquired resistance to these agents often occurs and thereby limits the clinical efficacy of monospecific targeted therapy. Results from both in vitro and in vivo studies indicate that cross-talk between EGFR and IGF-1R can lead to acquired resistance against EGFR-targeted drugs. This review describes the interface between the EGFR and IGF-1R signaling networks and the implications of the extensive cross-talk between these two receptor systems for cancer therapy. EGFR and IGF-1R interact on multiple levels, either through a direct association between the two receptors, by mediating the availability of each others ligands, or indirectly, via common interaction partners such as G protein coupled receptors (GPCR) or downstream signaling molecules. This multi-layered cross-talk and its involvement in the induction of resistance to targeted therapies provide a clear rationale for dual targeting of EGFR and IGF-1R. We discuss several (potential) strategies to simultaneously inhibit EGFR and IGF-1R signaling as promising novel therapeutic approaches.
Export Options
About this article
Cite this article as:
Veeken van der J., Oliveira S., Schiffelers M. R., Storm G., Henegouwen van Bergen en P.M.P. and Roovers C. R., Crosstalk Between Epidermal Growth Factor Receptor- and Insulin-Like Growth Factor-1 Receptor Signaling: Implications for Cancer Therapy, Current Cancer Drug Targets 2009; 9 (6) . https://dx.doi.org/10.2174/156800909789271495
DOI https://dx.doi.org/10.2174/156800909789271495 |
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
-
Theranostic Systems and Strategies for Monitoring Nanomedicine-Mediated Drug Targeting
Current Pharmaceutical Biotechnology Progress in Nutritional and Health Profile of Milk and Dairy Products: A Novel Drug Target
Endocrine, Metabolic & Immune Disorders - Drug Targets Function of miRNA in Controlling Drug Resistance of Human Cancers
Current Drug Targets Will Arsenic Trioxide Benefit Treatment of Solid Tumor by Nano- Encapsulation?
Mini-Reviews in Medicinal Chemistry <i>Uncaria tomentosa</i> (Willd. ex Schult.): Focus on Nutraceutical Aspects
Current Bioactive Compounds Advances in Transient Receptor Potential Vanilloid-2 Channel Expression and Function in Tumor Growth and Progression
Current Protein & Peptide Science <i>Arctium Lappa</i> and Management of Liver Functions to Detoxify the Bloodstream
The Natural Products Journal The Use of Anthracyclines for Therapy of CNS Tumors
Anti-Cancer Agents in Medicinal Chemistry Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation
Current Pharmacogenomics and Personalized Medicine Nanomedicines as Cancer Therapeutics: Current Status
Current Cancer Drug Targets The Urokinase Plasminogen Activator System: A Target for Anti-Cancer Therapy
Current Cancer Drug Targets Biomarkers of Angiogenesis and their Role in Patient Selection for Antiangiogenic Therapy
Current Angiogenesis (Discontinued) Gene Therapy of Cancer with Interleukin-12
Current Pharmaceutical Design Epigenetic Targets and their Inhibitors in Cancer Therapy
Current Topics in Medicinal Chemistry Telomerase Modulation in Therapeutic Approach
Current Pharmaceutical Design Tissue Transport of Anti-cancer Drugs
Current Pharmaceutical Design Killing Glioma ‘Stem-like’ Cells via Drug-Induced Relocation of Endosomal Urokinase Proteins
Anti-Cancer Agents in Medicinal Chemistry Pharmacologic Therapy for Cardiovascular Risk Reduction in Patients with the Metabolic Syndrome
Current Pharmaceutical Design The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs
Current Cancer Drug Targets Ribozymes in the Age of Molecular Therapeutics
Current Molecular Medicine