Abstract
The insulin-like growth factors (IGF) and their receptors play pivotal roles in cellular signaling transduction and thus regulate cell growth, differentiation, apoptosis, transformation and other important physiological progresses. The insulin-like growth factor 1 receptor (IGF-1R) mainly engages in the Ras/mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, and also forms cross-talk with the epidermal growth factor receptor (EGFR) pathway. Currently, it draws more attention since its overexpression has been demonstrated in various human cancers, such as colorectal cancer, breast cancer, prostate cancer and lung tumors, thus the strategy targeting the IGF-1R would be promising in treatment of these cancers. There are already dozens of agents developed for the inhibition of IGF-1R, which are categorized into monoclonal antibodies, small molecule inhibitors and so on. While in this review, small molecule inhibitors would be the focus for detailed discussion. Herein, we updated previously reported research papers and reviews in this field and summarized developments of small molecule inhibitors up to 2011. Finally, we proposed the application of network pharmacology methods to reconsider the clinical use of inhibitors with concomitant IR inhibition or other kinases inhibition, hoping that more optimal combinations would be obtained for cancer therapy.
Keywords: Receptor tyrosine kinase, IGF-1R, IR, EGFR, small molecule inhibitors, anticancer strategies, signaling transduction pathway, network pharmacology, cell growth, apoptosis
Current Pharmaceutical Design
Title:Insulin-like Growth Factor-1 Receptor (IGF-1R) Kinase Inhibitors in Cancer Therapy: Advances and Perspectives
Volume: 18 Issue: 20
Author(s): Mengzhu Xue, Xianwen Cao, Ye Zhong, Dong Kuang, Xiaofeng Liu, Zhenjiang Zhao and Honglin Li
Affiliation:
Keywords: Receptor tyrosine kinase, IGF-1R, IR, EGFR, small molecule inhibitors, anticancer strategies, signaling transduction pathway, network pharmacology, cell growth, apoptosis
Abstract: The insulin-like growth factors (IGF) and their receptors play pivotal roles in cellular signaling transduction and thus regulate cell growth, differentiation, apoptosis, transformation and other important physiological progresses. The insulin-like growth factor 1 receptor (IGF-1R) mainly engages in the Ras/mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, and also forms cross-talk with the epidermal growth factor receptor (EGFR) pathway. Currently, it draws more attention since its overexpression has been demonstrated in various human cancers, such as colorectal cancer, breast cancer, prostate cancer and lung tumors, thus the strategy targeting the IGF-1R would be promising in treatment of these cancers. There are already dozens of agents developed for the inhibition of IGF-1R, which are categorized into monoclonal antibodies, small molecule inhibitors and so on. While in this review, small molecule inhibitors would be the focus for detailed discussion. Herein, we updated previously reported research papers and reviews in this field and summarized developments of small molecule inhibitors up to 2011. Finally, we proposed the application of network pharmacology methods to reconsider the clinical use of inhibitors with concomitant IR inhibition or other kinases inhibition, hoping that more optimal combinations would be obtained for cancer therapy.
Export Options
About this article
Cite this article as:
Xue Mengzhu, Cao Xianwen, Zhong Ye, Kuang Dong, Liu Xiaofeng, Zhao Zhenjiang and Li Honglin, Insulin-like Growth Factor-1 Receptor (IGF-1R) Kinase Inhibitors in Cancer Therapy: Advances and Perspectives , Current Pharmaceutical Design 2012; 18 (20) . https://dx.doi.org/10.2174/138161212800672723
DOI https://dx.doi.org/10.2174/138161212800672723 |
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
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
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
GPR55, a Lysophosphatidylinositol Receptor with Cannabinoid Sensitivity?
Current Topics in Medicinal Chemistry Heat Shock Protein 90 – a Potential Target in the Treatment of Human Acute Myelogenous Leukemia
Current Cancer Drug Targets Insights Into Effects of Ellagic Acid on the Nervous System: A Mini Review
Current Pharmaceutical Design Effects of Eugenol on the Central Nervous System: Its Possible Application to Treatment of Alzheimers Disease, Depression, and Parkinsons Disease
Current Bioactive Compounds Clinical Management of Infectious Diarrhea
Reviews on Recent Clinical Trials Unusual Food Allergy: AlioideaAllergic Reactions Overview
Recent Patents on Inflammation & Allergy Drug Discovery A Systematic Evaluation of Solubility Enhancing Excipients to Enable the Generation of Permeability Data for Poorly Soluble Compounds in Caco-2 Model
Drug Metabolism Letters Cytotoxic and Apoptotic Effect of <i>Iris taochia</i> Plant Extracts on Human Breast Cancer (MCF-7) Cells
Current Proteomics DNA Recognition by a Novel Bis-Intercalator, Potent Anticancer Drug XR5944
Current Topics in Medicinal Chemistry Biodistribution, Safety and Organ Toxicity of Docetaxel-Loaded in HER-2 Aptamer Conjugated Ecoflex® Nanoparticles in a Mouse Xenograft Model of Ovarian Cancer
Recent Patents on Nanotechnology Pistachio Green Hull Extract Induces Apoptosis through Multiple Signaling Pathways by Causing Oxidative Stress on Colon Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Fluorescent Molecular Imaging: Technical Progress and Current Preclinical and Clinical Applications in Urogynecologic Diseases
Current Molecular Medicine Chemoprevention Strategies for High Risk Women
Current Women`s Health Reviews Molecular Aspects of FKBP51 that Enable Melanoma Dissemination
Current Molecular Pharmacology Transcriptional Regulation of the p53 Tumor Suppressor Gene: A Potential Target for Cancer Therapeutics?
Recent Patents on DNA & Gene Sequences Serum Carboxypeptidase N1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Activin Receptor-Like Kinase 1: a Novel Anti-angiogenesis Target from TGF-β Family
Mini-Reviews in Medicinal Chemistry Developments in the Application of 1,2,3-Triazoles in Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Interactions Between Cholinergic and Fibroblast Growth Factor Receptors in Brain Trophism and Plasticity
Current Protein & Peptide Science PET Imaging of Steroid Receptor Expression in Breast and Prostate Cancer
Current Pharmaceutical Design