Abstract
IGF-IR (Insulin-like growth factor receptor 1) is a tetrameric glycoprotein composed of two α and two β subunits. The α subunit localizes extra-cellularly for ligand binding, whereas the β subunit consists of transmembrane chains and a cytoplasmic tyrosine kinase domain for enzymatic activity. IGF-IR ligands, IGF-I and IGF-II, are mitogens and survival factors for many cancer cells. Binding of ligands to the IGF-IR initiates a cascade of events leading to activation of signal transduction pathways, mainly MAPK and PI-3K pathways, to stimulate proliferation / mitogenesis, to induce neoplastic transformation, to inhibit apoptosis, and to promote angiogenesis and metastasis. It has been shown that the presence of IGF-IR was required for transformation induced by many oncogenes and over-expression or constitutive activation of IGF-IR gave rise to transformed phenotypes. Significantly, over-expression of IGF-IR was observed in multiple human cancers including carcinomas of breast, lung, colon, and prostate. Patients with IGF-IR positive cancers had a worse prognosis in some cases. Furthermore, down-regulation or functional inactivation of IGF-IR sensitized tumor cells to apoptosis and reversed tumor cell phenotype. Thus, IGF-IR appears to be a promising cancer target. Indeed, a variety of approaches aimed at targeting IGF-IR have been utilized to prove the concept, or are being developed for potential anticancer therapies. These include targeting functional IGF-IR on cell surface, targeting ligand / receptor interaction, targeting receptor expression and functions, and targeting receptor kinase activity. Cancer patients could eventually benefit from the development of these specific IGF-IR antagonists.
Keywords: anti-cancer target, inducing apoptosis, angiogenesis and metastasis, biological outcomes, igf-ir expression, transformation, cysteine protease inhibitor, autophosphorylation
Current Cancer Drug Targets
Title: Insulin-Like Growth Factor Receptor-1 as an Anti-Cancer Target: Blocking Transformation and Inducing Apoptosis
Volume: 2 Issue: 3
Author(s): Yuli Wang and Yi Sun
Affiliation:
Keywords: anti-cancer target, inducing apoptosis, angiogenesis and metastasis, biological outcomes, igf-ir expression, transformation, cysteine protease inhibitor, autophosphorylation
Abstract: IGF-IR (Insulin-like growth factor receptor 1) is a tetrameric glycoprotein composed of two α and two β subunits. The α subunit localizes extra-cellularly for ligand binding, whereas the β subunit consists of transmembrane chains and a cytoplasmic tyrosine kinase domain for enzymatic activity. IGF-IR ligands, IGF-I and IGF-II, are mitogens and survival factors for many cancer cells. Binding of ligands to the IGF-IR initiates a cascade of events leading to activation of signal transduction pathways, mainly MAPK and PI-3K pathways, to stimulate proliferation / mitogenesis, to induce neoplastic transformation, to inhibit apoptosis, and to promote angiogenesis and metastasis. It has been shown that the presence of IGF-IR was required for transformation induced by many oncogenes and over-expression or constitutive activation of IGF-IR gave rise to transformed phenotypes. Significantly, over-expression of IGF-IR was observed in multiple human cancers including carcinomas of breast, lung, colon, and prostate. Patients with IGF-IR positive cancers had a worse prognosis in some cases. Furthermore, down-regulation or functional inactivation of IGF-IR sensitized tumor cells to apoptosis and reversed tumor cell phenotype. Thus, IGF-IR appears to be a promising cancer target. Indeed, a variety of approaches aimed at targeting IGF-IR have been utilized to prove the concept, or are being developed for potential anticancer therapies. These include targeting functional IGF-IR on cell surface, targeting ligand / receptor interaction, targeting receptor expression and functions, and targeting receptor kinase activity. Cancer patients could eventually benefit from the development of these specific IGF-IR antagonists.
Export Options
About this article
Cite this article as:
Wang Yuli and Sun Yi, Insulin-Like Growth Factor Receptor-1 as an Anti-Cancer Target: Blocking Transformation and Inducing Apoptosis, Current Cancer Drug Targets 2002; 2 (3) . https://dx.doi.org/10.2174/1568009023333863
DOI https://dx.doi.org/10.2174/1568009023333863 |
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
-
TNF as a Target of Inflammation in Rheumatoid Arthritis
Endocrine, Metabolic & Immune Disorders - Drug Targets Diet and Dysfunctional Metabolism in BB Rats
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Critical Questions for Preclinical Trials on Safety and Efficacy of Vascular Endothelial Growth Factor-Based Therapeutic Angiogenesis for Ischemic Stroke
CNS & Neurological Disorders - Drug Targets Amyloid-beta Targeted Therapeutic Approaches for Alzheimer’s Disease: Long Road Ahead
Current Drug Targets Is Erectile Dysfunction an Example of Abnormal Endothelial Function?
Current Vascular Pharmacology Design and Development of Preservative Free Herbal Dosage Forms
The Natural Products Journal High-Density Lipoprotein-Raising Strategies: Update 2010
Current Pharmaceutical Design Linagliptin: A Novel Methylxanthin Based Approved Dipeptidyl Peptidase-4 Inhibitor
Current Drug Targets Side Effects of Atypical Antipsychotic Drugs
Current Pharmaceutical Design The Potentials of Uncariae Ramulus Cum Uncis for the Treatment of Migraine: Targeting CGRP in the Trigeminovascular System
Current Neuropharmacology Targeting Exocytosis: Ins and Outs of the Modulation of Quantal Dopamine Release
CNS & Neurological Disorders - Drug Targets Neuroprotection and Hypothermia in Infants and Children
Current Drug Targets The Putative Adverse Effects of Bisphenol A on Autoimmune Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Secreted Nucleobindin-2 Inhibits 3T3-L1 Adipocyte Differentiation
Protein & Peptide Letters Insulin Resistance in Diabetes: Present and Future Prospective of Treatment
Current Psychopharmacology Inhibiting the Enzymes of the Endothelin and Renin-Angiotensin Systems in Cancer
Current Enzyme Inhibition Subject Index To Volume 6
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Occurrence of Bisphenol A, Phthalates, Parabens and Other Environmental Phenolic Compounds in House Dust: A Review
Current Organic Chemistry Endothelin and Its Receptor Interactions: Role of Extracellular Receptor Domain and Length of Peptide Ligands
Protein & Peptide Letters Sodium Dependent Multivitamin Transporter (SMVT): A Potential Target for Drug Delivery
Current Drug Targets