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
-
Nucleic Acids as Therapeutic Agents
Current Topics in Medicinal Chemistry MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Ovarian Cancer
Recent Patents on Biomarkers The Complexity of Aging: Cancer Risk Among Elderly People and Infectious Risk Among Those with Cancer
Anti-Cancer Agents in Medicinal Chemistry Kinase Inhibitors Targeting Anti-angiogenesis as Anti-cancer Therapies
Current Angiogenesis (Discontinued) Omega-3 Fatty Acid Treatment Combined with Chemotherapy to Prevent Toxicity, Drug Resistance, and Metastasis in Cancer
Current Drug Targets CCL2-CCR2 Signaling in Disease Pathogenesis
Endocrine, Metabolic & Immune Disorders - Drug Targets HDACs and HDAC Inhibitors in Urothelial Carcinoma – Perspectives for an Antineoplastic Treatment
Current Medicinal Chemistry Free Radical Attack on Cholesterol: Oxysterols as Markers of Oxidative Stress and as Bioactive Molecules
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Anti-Proliferative Role of the Tyrosine Kinase Inhibitors TKI-258 on Oral Squamous Cell Carcinoma In Vitro
Anti-Cancer Agents in Medicinal Chemistry How to Inhibit Telomerase Activity for Cancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Regenerative Potential of Stem Cell-derived Extracellular Vesicles in Spinal Cord Injury (SCI)
Current Stem Cell Research & Therapy Use of Metallomics in Environmental Pollution Assessment Using Mice Mus musculus/Mus spretus as Bioindicators
Current Analytical Chemistry Perspectives for Novel Mixed Diruthenium-Organic Drugs as Metallopharmaceuticals in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry 177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma
Current Radiopharmaceuticals Cardiotoxicity of Molecularly Targeted Agents
Current Cardiology Reviews UDP-Glucuronosyltransferases
Current Drug Metabolism Peroxisome Proliferator-Activated Receptor-γ and Its Ligands in the Treatment of Tumors in the Nervous System
Current Stem Cell Research & Therapy Possibilities of Poly(D,L-lactide-co-glycolide) in the Formulation of Nanomedicines Against Cancer
Current Drug Targets Evolutioninthe Pharmacogenetics and Pharmacogenomics of Inflammatory Bowel Disease - Order Slowly Rises from the Chaos
Current Pharmacogenomics Exosomes: A Role for Naturally Occurring Nanovesicles in Cancer Growth, Diagnosis and Treatment
Current Gene Therapy