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.
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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 |
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