AVE8062: A new combretastatin derivative vascular disrupting agent

Angelo Delmonte, Cristiana Sessa

Research output: Contribution to journalArticlepeer-review

Abstract

Angiogenesis has an essential role in promoting and supporting tumor growth and it is an important therapeutic target. The tumor vascular network is the result of pro-angiogenic and inhibitory factors as well as of the interaction between endothelial cells and extracellular matrix. Different antiangiogenic therapeutics have been developed to improve tumor control through vascular-targeting agents (VTA). VTAs can be divided into two groups: antiangiogenic agents and vascular-disrupting agents (VDAs). VTAs inhibit specific factors required to induce and direct the angiogenic process, with major activity against small tumor masses and at the tumor periphery, encompassing monoclonal antibodies and small molecules inhibitors of the tyrosine kinase domain of the VEGF receptor. VDAs specifically target and destroy well-established tumor vessels with ischemia and destruction of large masses with central hemorrhagic necrosis and survival of a thin peripheral tumor layer. VDAs can be divided into biologics, such as ligandbased, and small-molecule agents; this second group includes small-molecule VDAs like flavonoids, such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA), and microtubule-destabilizing agents. In this review we will discuss the mechanism of action, as well as the preclinical and clinical results, of one of the most promising antitubulin agents: the combretastatin A4-phosphate derivative, AVE8062A.

Original languageEnglish
Pages (from-to)1541-1548
Number of pages8
JournalExpert Opinion on Investigational Drugs
Volume18
Issue number10
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Angiogenesis
  • Antivascular disrupting agents
  • New drugs
  • Solid tumor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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