Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy.
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Strebhardt K
Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy.
Nat Rev Drug Discov. 2010 Aug;9(8):643-60. doi: 10.1038/nrd3184.
- PubMed ID
- 20671765 [ View in PubMed]
- Abstract
The polo-like kinase 1 (PLK1) acts in concert with cyclin-dependent kinase 1-cyclin B1 and Aurora kinases to orchestrate a wide range of critical cell cycle events. Because PLK1 has been preclinically validated as a cancer target, small-molecule inhibitors of PLK1 have become attractive candidates for anticancer drug development. Although the roles of the closely related PLK2, PLK3 and PLK4 in cancer are less well understood, there is evidence showing that PLK2 and PLK3 act as tumour suppressors through their functions in the p53 signalling network, which guards the cell against various stress signals. In this article, recent insights into the biology of PLKs will be reviewed, with an emphasis on their role in malignant transformation, and progress in the development of small-molecule PLK1 inhibitors will be examined.