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 β subunit of α/β 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 vasculardisrupting 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.
Keywords: Microtubule, microtubule-targeting agents, endothelial cell, angiogenesis, anti-vascular therapy, metronomic chemotherapy
Current Cancer Drug Targets
Title: Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment
Volume: 7 Issue: 6
Author(s): Eddy Pasquier, Nicolas Andre and Diane Braguer
Affiliation:
Keywords: Microtubule, microtubule-targeting agents, endothelial cell, angiogenesis, anti-vascular therapy, metronomic chemotherapy
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 β subunit of α/β 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 vasculardisrupting 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.
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Cite this article as:
Pasquier Eddy, Andre Nicolas and Braguer Diane, Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment, Current Cancer Drug Targets 2007; 7 (6) . https://dx.doi.org/10.2174/156800907781662266
DOI https://dx.doi.org/10.2174/156800907781662266 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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