Abstract
This review will focus on the emerging role of the insulin receptor (IR) in cancer. Several epidemiological studies have shown that insulin resistance states, characterized by hyperinsulinemia, are associated with an increased risk for a number of malignancies, including carcinomas of the breast, prostate, colon and kidney. Recent data have elucidated some molecular mechanisms by which IR is involved in cancer. First, IR is overexpressed in several human malignancies. Interestingly, one of the two IR isoform (IR-A) is especially overexpressed in cancer. IR-A is the IR fetal isoform and has the peculiar characteristic to bind not only insulin but also IGF-II. Second, IR forms hybrid receptors with the homologous IGF-IR, which is also commonly overexpressed in cancer. These hybrid receptors containing IR-A hemidimers have broad binding specificity as they bind IGF-I and also IGF-II and insulin. By binding to hybrid receptors, insulin may stimulate specific IGF-IR signaling pathways. Overexpression of IR-A is, therefore, a major mechanism of IGF system overactivation in cancer. These findings may have important implications for both the prevention and treatment of common human malignancies. They underline the concept that hyperinsulinemia, associated with insulin resistance and obesity, should be treated by changes in life style and/or pharmachological approaches to avoid an increased risk for cancer. IR-A isoform and hybrid receptors should be regarded, therefore, as potential molecular targets for novel anti-cancer therapies.
Keywords: Insulin receptor, hybrid receptors, IGF-I receptor, endocrine related cancers, isoforms, differentiation, transformation, anticancer therapy
Current Pharmaceutical Design
Title: The Role of Insulin Receptor Isoforms and Hybrid Insulin/IGF-I Receptors in Human Cancer
Volume: 13 Issue: 7
Author(s): Antonino Belfiore
Affiliation:
Keywords: Insulin receptor, hybrid receptors, IGF-I receptor, endocrine related cancers, isoforms, differentiation, transformation, anticancer therapy
Abstract: This review will focus on the emerging role of the insulin receptor (IR) in cancer. Several epidemiological studies have shown that insulin resistance states, characterized by hyperinsulinemia, are associated with an increased risk for a number of malignancies, including carcinomas of the breast, prostate, colon and kidney. Recent data have elucidated some molecular mechanisms by which IR is involved in cancer. First, IR is overexpressed in several human malignancies. Interestingly, one of the two IR isoform (IR-A) is especially overexpressed in cancer. IR-A is the IR fetal isoform and has the peculiar characteristic to bind not only insulin but also IGF-II. Second, IR forms hybrid receptors with the homologous IGF-IR, which is also commonly overexpressed in cancer. These hybrid receptors containing IR-A hemidimers have broad binding specificity as they bind IGF-I and also IGF-II and insulin. By binding to hybrid receptors, insulin may stimulate specific IGF-IR signaling pathways. Overexpression of IR-A is, therefore, a major mechanism of IGF system overactivation in cancer. These findings may have important implications for both the prevention and treatment of common human malignancies. They underline the concept that hyperinsulinemia, associated with insulin resistance and obesity, should be treated by changes in life style and/or pharmachological approaches to avoid an increased risk for cancer. IR-A isoform and hybrid receptors should be regarded, therefore, as potential molecular targets for novel anti-cancer therapies.
Export Options
About this article
Cite this article as:
Belfiore Antonino, The Role of Insulin Receptor Isoforms and Hybrid Insulin/IGF-I Receptors in Human Cancer, Current Pharmaceutical Design 2007; 13 (7) . https://dx.doi.org/10.2174/138161207780249173
DOI https://dx.doi.org/10.2174/138161207780249173 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
![](/images/wayfinder.jpg)
- 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
- Announcements
Related Articles
-
Therapeutic Potential and Pharmaceutical Applications of <i>Cucurbita</i>
Current Nutrition & Food Science Energetics of Quadruplex-Drug Recognition in Anticancer Therapy
Current Cancer Drug Targets Cardiac (myo)fibroblast: Novel Strategies for its Targeting Following Myocardial Infarction
Current Pharmaceutical Design Retraction Notice to Role of Vitamin K2 in the Treatment of Postmenopausal Osteoporosis
Current Drug Safety The Insulin-Like Growth Factor (IGF) Signaling Pathway: Strategies for Successful Therapeutic Tasks in Cancer Treatment
Current Cancer Therapy Reviews Dehydroandrographolide Inhibits Osteosarcoma Cell Growth and Metastasis by Targeting SATB2-mediated EMT
Anti-Cancer Agents in Medicinal Chemistry The Role of Reactive Oxygen Species in Tumor Treatment and its Impact on Bone Marrow Hematopoiesis
Current Drug Targets Molecular Imaging of Cancer with Radiolabeled Peptides and PET
Anti-Cancer Agents in Medicinal Chemistry Polyethyleneimine-Based Nanocarriers for Gene Delivery
Current Pharmaceutical Design Non-Analgesic Effects of Opioids: The Interaction of Opioids with Bone and Joints
Current Pharmaceutical Design Interplay between LncRNA/miRNA and TGF-β Signaling in the Tumorigenesis of Gynecological Cancer
Current Pharmaceutical Design CDK9 as an Appealing Target for Therapeutic Interventions
Current Drug Targets Effect of Oxidative Stress on the Pharmacokinetics of Clomipramine in Rats Treated with Ferric-Nitrilotriacetate
Drug Metabolism Letters Modulation of Tumour-Related Signaling Pathways by Natural Pentacyclic Triterpenoids and their Semisynthetic Derivatives
Current Medicinal Chemistry Follow the ATP: Tumor Energy Production: A Perspective
Anti-Cancer Agents in Medicinal Chemistry Cell Cycle and Cancer: The G1 Restriction Point and the G1 / S Transition
Current Genomics HSP90-regulated CHIP/TRIM21/p21 Axis Involves in the Senescence of Osteosarcoma Cells
Protein & Peptide Letters Finding Appropriate Signal Peptides for Secretory Production of Recombinant Glucarpidase: An <i>In Silico</i> Method
Recent Patents on Biotechnology Current Phthalocyanines Delivery Systems in Photodynamic Therapy: An Updated Review
Current Medicinal Chemistry Antioxidant Response of Osteoblasts to Doxycycline in an Inflammatory Model Induced by C-reactive Protein and Interleukin-6
Infectious Disorders - Drug Targets