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Lookup NU author(s): Dr Gajanan Sherbet
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© 2017 Elsevier B.V. The search for small molecule inhibitors has gained prominence with the recognition of their inherent advantage for cancer therapy. Combretastatin is a naturally occurring small stilbenoid. By virtue of the ability to bind to tubulin combretastatin and its derivatives promote depolymerisation of microtubules as well as inhibit tubulin polymerisation. This suppresses cell proliferation signalling and induces apoptosis. Combretastatins activate mitotic checkpoints that lead to mitotic catastrophe and apoptosis. They subvert the signalling systems which stimulate invasion, activate EMT (epithelial mesenchyme transition) and promote tumour progression. Allied with the ability to suppress angiogenesis these compounds have been viewed as potential inhibitors of metastasis. The notion of merging RTK (receptor tyrosine kinase) inhibition with suppression of invasion and possible inhibition of EMT has contributed to the credibility of combretastatins as anti-cancer agents. Invaluable are their attributes of inhibiting tumour growth and induction of apoptosis and necrosis by reducing blood supply to the tumour. Aside from these biological effects, this commentary also discusses the issues of the targeting of combretastatins to the tumour vasculature and effective delivery of the drugs encapsulated in nanospheres. Notwithstanding the perceived benefits, one can see a compelling need to understand the effects of combretastatin on the actin cytoskeletal dynamics and the disruption of microtubule polymerisation, and whether it is more efficient a tumour inhibitor than the conventional drugs that target microtubule dynamics. Combinations of combretastatins with other vascular disrupting agents have been attempted. It is essential to establish the perceived inhibition of EMT beyond reasonable doubt. This might justify using the combretastatins with allosteric EMT and Akt inhibitors as additional choices for pre-clinical/clinical studies.
Author(s): Sherbet GV
Publication type: Note
Publication status: Published
Journal: Cancer Letters
Year: 2017
Volume: 403
Pages: 289-295
Print publication date: 10/09/2017
Online publication date: 06/07/2017
Acceptance date: 28/06/2017
ISSN (print): 0304-3835
ISSN (electronic): 1872-7980
Publisher: Elsevier Ireland Ltd
URL: https://doi.org/10.1016/j.canlet.2017.06.032
DOI: 10.1016/j.canlet.2017.06.032
