Abstract
Various cancer types have different molecular and biological strategies for vascularization: neoangiogenesis, postnatal vasculogenesis, glomeruloid angiogenesis, intussusceptive microvascular growth, vessel cooption and vascular mimicry. The majority is still relatively obscure, which limits the development of more successful antivascular agents. It is not a surprise that, as our knowledge is deepest in case of tumor-induced neoangiogenesis, the first successful antiangiogenic drugs have been developed in this area. As neoangiogenesis involves growth factor receptors, most of them tyrosine kinases (KIT, Flt-3, VEGFRs, PDGFR, TIE2, FGFR1, EGFR and MET), several of these novel agents are tyrosine kinase inhibitors. This review summarizes our recent knowledge on various forms of cancer vascularization, the molecular mechanisms behind, depicting the “drugable” targets. In a short overview, we demonstrate the array of antiangiogenic approaches focusing on the tyrosine kinase inhibitors and summarize their preclinical activities. Finally we review the clinically available antiangiogenic tyrosine kinase inhibitors and demonstrate their current application and future perspectives. Further development in this field may depend on the identification of novel inhibitors targeting kinases that cannot be modulated yet by the available agents and on the development of vascularization strategy-specific design of these antivascular therapies.
Keywords: Tumor vascularization, antivascular therapy, tyrosine kinases, kinase inhibitors
Anti-Cancer Agents in Medicinal Chemistry
Title: Antiangiogenic Drugs and Tyrosine Kinases
Volume: 8 Issue: 5
Author(s): Jozsef Timar and Balazs Dome
Affiliation:
Keywords: Tumor vascularization, antivascular therapy, tyrosine kinases, kinase inhibitors
Abstract: Various cancer types have different molecular and biological strategies for vascularization: neoangiogenesis, postnatal vasculogenesis, glomeruloid angiogenesis, intussusceptive microvascular growth, vessel cooption and vascular mimicry. The majority is still relatively obscure, which limits the development of more successful antivascular agents. It is not a surprise that, as our knowledge is deepest in case of tumor-induced neoangiogenesis, the first successful antiangiogenic drugs have been developed in this area. As neoangiogenesis involves growth factor receptors, most of them tyrosine kinases (KIT, Flt-3, VEGFRs, PDGFR, TIE2, FGFR1, EGFR and MET), several of these novel agents are tyrosine kinase inhibitors. This review summarizes our recent knowledge on various forms of cancer vascularization, the molecular mechanisms behind, depicting the “drugable” targets. In a short overview, we demonstrate the array of antiangiogenic approaches focusing on the tyrosine kinase inhibitors and summarize their preclinical activities. Finally we review the clinically available antiangiogenic tyrosine kinase inhibitors and demonstrate their current application and future perspectives. Further development in this field may depend on the identification of novel inhibitors targeting kinases that cannot be modulated yet by the available agents and on the development of vascularization strategy-specific design of these antivascular therapies.
Export Options
About this article
Cite this article as:
Timar Jozsef and Dome Balazs, Antiangiogenic Drugs and Tyrosine Kinases, Anti-Cancer Agents in Medicinal Chemistry 2008; 8 (5) . https://dx.doi.org/10.2174/187152008784533035
DOI https://dx.doi.org/10.2174/187152008784533035 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
Drug Targeting Strategies for Photodynamic Therapy
Anti-Cancer Agents in Medicinal Chemistry Radiogenetic Therapy: Strategies to Overcome Tumor Resistance
Current Pharmaceutical Design Merging Transport Data for Choroid Plexus with Blood-Brain Barrier to Model CNS Homeostasis and Disease More Effectively
CNS & Neurological Disorders - Drug Targets Induced pluripotent stem cell-derived mesenchymal stem cells: A leap toward personalized therapies.
Current Stem Cell Research & Therapy Impact of Cellular Senescence in Aging and Cancer
Current Pharmaceutical Design Role of Cannabinoids and Endocannabinoids in Cerebral Ischemia
Current Pharmaceutical Design Biological Relevance of DNA Polymerase Beta and Translesion Synthesis Polymerases to Cancer and its Treatment
Current Molecular Pharmacology Advances in Drug Delivery from Nose to Brain: An Overview
Current Drug Therapy Telomerase Inhibition in Cancer Therapeutics: Molecular-Based Approaches
Current Medicinal Chemistry Radiation-Induced Stress Proteins - the Role of Heat Shock Proteins (HSP) in Anti- Tumor Responses
Current Medicinal Chemistry An Insight into Drug Repositioning for the Development of Novel Anti-Cancer Drugs
Current Topics in Medicinal Chemistry A Hybrid Discrete Imperialist Competition Algorithm for Gene Selection for Microarray Data
Current Proteomics Biotin-Encoded and Fe<sub>3</sub>O<sub>4</sub>-Loaded Polymeric Nano Micelles: Preparation, Optimization and In Vitro Characterization
Letters in Drug Design & Discovery Nitric Oxide and Cancer Therapy: The Emperor has NO Clothes
Current Pharmaceutical Design The Synergistic Cytotoxic and Apoptotic Effect of Resveratrol and Naringenin on Y79 Retinoblastoma Cell Line
Anti-Cancer Agents in Medicinal Chemistry New Functions of the Inositol Polyphosphate 5-Phosphatases in Cancer
Current Pharmaceutical Design Patent Selections:
Recent Patents on Inflammation & Allergy Drug Discovery Resveratrol in Cancer: Cellular and Mitochondrial Consequences of Proton Transport Inhibition
Current Pharmaceutical Design Targeted Taxane Delivery Systems: Recent Advances
Drug Delivery Letters Genetic Chemoprotection with Mutant O6-Alkylguanine-DNA-Alkyltransferases
Current Gene Therapy