Drugging Cell Cycle Kinases in Cancer Therapy

Author(s): S. Blagden, J. de Bono

Journal Name: Current Drug Targets

Volume 6 , Issue 3 , 2005

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Abstract:

Cell cycle kinases are comprised of cyclin-dependent kinases (Cdks), non-Cdk kinases such as Plk-1 and Aurora and checkpoint proteins such as Chk1 and Chk2. Though ubiquitous to dividing cells, many cell cycle kinases are amplified or over-expressed in malignancy and are potential targets for anti-cancer therapies. Cdk inhibiting drugs (such as flavopiridol, UCN-01, E7070, R-Roscovitine and BMS-387032) have shown preclinical and clinical anticancer activity. However, many of these agents are promiscuous and undiscerning, targeting other non-cell cycle kinases and affecting normal cells, thereby causing significant toxicity. To overcome this, a new generation of Cdk inhibitors are in development with greater target specificity, as well as others that inhibit non-Cdk cell cycle kinases, both directly and indirectly. The outcome of early clinical trials involving these agents is awaited, but these certainly represent a promising new area of anticancer drug development.

Keywords: cyclin dependent kinase inhibitors, aurora, polo-like kinase

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Article Details

VOLUME: 6
ISSUE: 3
Year: 2005
Page: [325 - 335]
Pages: 11
DOI: 10.2174/1389450053765824
Price: $65

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