Targeting microtubules to inhibit angiogenesis and disrupt tumour vasculature: implications for cancer treatment.

Abstract

Anticancer agents that interfere with tubulin functions are widely used in the clinic and have a broad spectrum of activity against both haematological malignancies and solid tumours. These Microtubule-Targeting Agents (MTAs), such as the taxanes and Vinca alkaloids, bind to the beta subunit of alpha/beta tubulin and disrupt microtubule dynamics in tumour cells, ultimately leading to mitotic block and subsequent cell death. Recently, MTAs have received considerable interest as potential tumour-selective anti-angiogenic and vascular-disrupting agents. Angiogenesis is a keystone of tumour progression and metastasis and targeting the formation of new blood vessels within the tumour is therefore regarded as a promising strategy for cancer therapy. In this regard, conventional MTAs can be given on daily schedules at non-toxic doses (metronomic dosing) to disturb tumour angiogenesis. Some MTAs can also act as vascular-disrupting agents. After briefly reviewing the classical mechanisms involved in the anti-tumour action of MTAs, we will focus on the latest studies investigating the molecular and cellular processes underlying the anti-angiogenic and the vascular-disrupting properties of these agents. We will also review and discuss the potential clinical development and the limitations of MTAs used as tumour-specific anti-vascular molecules.

• Authors: Eddy Pasquier, Nicolas André, Diane Braguer
• Journal: Current cancer drug targets (Curr Cancer Drug Targets) Vol. 7 Issue 6 Pg. 566-81 (Sep 2007) ISSN: 1873-5576 [Electronic] Netherlands
• PMID: 17896922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Angiogenesis Inhibitors

Topics

• Angiogenesis Inhibitors (pharmacology, therapeutic use)
• Humans
• Microtubules (drug effects)
• Neoplasms (blood supply, drug therapy)
• Neovascularization, Pathologic (prevention & control)