Targeting microtubules to inhibit angiogenesis and disrupt tumour vasculature: implications for cancer treatment.
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.
Pasquier
Eddy
E
FRE-CNRS 2737, CISMET (Cytosquelette et Intégration des Signaux du Micro-Environnement Tumoral), University of Aix-Marseille, 27 bd Jean Moulin, 13005 Marseille, France.
André
Nicolas
N
Braguer
Diane
D
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*
D020533:Angiogenesis Inhibitors