Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy

Rath, N. and Olson, M.F. (2012) Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy. EMBO Reports, 13(10), pp. 900-908. (doi: 10.1038/embor.2012.127)

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Abstract

The Rho-associated (ROCK) serine/threonine kinases have emerged as central regulators of the actomyosin cytoskeleton, their main purpose being to promote contractile force generation. Aided by the discovery of effective inhibitors such as Y27632, their roles in cancer have been extensively explored with particular attention focused on motility, invasion and metastasis. Recent studies have revealed a surprisingly diverse range of functions of ROCK. These insights could change the way ROCK inhibitors might be used in cancer therapy to include the targeting of stromal rather than tumour cells, the concomitant blocking of ROCK and proteasome activity in K-Ras-driven lung cancers and the combination of ROCK with tyrosine kinase inhibitors for treating haematological malignancies such as chronic myeloid leukaemia. Despite initial optimism for therapeutic efficacy of ROCK inhibition for cancer treatment, no compounds have progressed into standard therapy so far. However, by carefully defining the key cancer types and expanding the appreciation of ROCK's role in cancer beyond being a cell-autonomous promoter of tumour cell invasion and metastasis, the early promise of ROCK inhibitors for cancer therapy might still be realized.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rath, Dr Nicola and Olson, Professor Michael
Authors: Rath, N., and Olson, M.F.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:EMBO Reports
ISSN:1469-221X
Published Online:11 September 2012
Published Online:11 September 2012

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