Anticancer strategies involving the vasculature
- 7 May 2009
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Clinical Oncology
- Vol. 6 (7), 395-404
- https://doi.org/10.1038/nrclinonc.2009.52
Abstract
Understanding the process of tumor angiogenesis and ways to modify this is a key point in the fight against cancer. This Review explores the current status of vascular-disrupting strategies, discusses how anti-VEGF-based anti-angiogenic therapies can be combined with conventional chemotherapy and radiotherapy, and highlights potential future targets for therapeutic intervention. The growth and metastasis of solid tumors critically depends on their ability to develop their own blood supply, a process known as tumor angiogenesis. Over the past decade much work has been performed to understand this process, and modifying this process provides a key point of therapeutic intervention in the fight against cancer. This Review explores the development of anti-VEGF-based antiangiogenic therapies, of which there are currently three licensed for clinical use worldwide. Although originally anticipated to inhibit the growth of tumor vessels, the induction of vascular normalization caused by these approved agents has provided a novel means of effective delivery of known chemotherapeutic agents. The development of small molecules that target VEGF receptors has resulted in the generation of inhibitors with not only vascular activity but antitumor activity in certain cancers. This Review will address the current status of vascular-disrupting strategies, such as therapies designed to induce tumor collapse by selectively destroying existing tumor vessels. These therapies can be broadly divided into small-molecular-weight vascular-disrupting agents and ligand-directed approaches. We discuss the current status of development, drug mechanisms of actions, combination with conventional chemotherapy and radiotherapy, and potential future targets for therapeutic intervention.Keywords
This publication has 99 references indexed in Scilit:
- Cilengitide: an integrin-targeting arginine–glycine–aspartic acid peptide with promising activity for glioblastoma multiformeExpert Opinion on Investigational Drugs, 2008
- A novel method of differential gene expression analysis using multiple cDNA libraries applied to the identification of tumour endothelial genesBMC Genomics, 2008
- Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesisGenes & Development, 2007
- Antiangiogenics: The Potential Role of Integrating This Novel Treatment Modality With Chemoradiation for Solid CancersJournal of Clinical Oncology, 2007
- Genes that Distinguish Physiological and Pathological AngiogenesisCancer Cell, 2007
- Mechanisms of adverse effects of anti-VEGF therapy for cancerBritish Journal of Cancer, 2007
- AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma PatientsCancer Cell, 2007
- VEGF receptor signalling ? in control of vascular functionNature Reviews Molecular Cell Biology, 2006
- Antibody Pretargeting Advances Cancer Radioimmunodetection and RadioimmunotherapyJournal of Clinical Oncology, 2006
- Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical ResultsJournal of Clinical Oncology, 2005