Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy.
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.
Strebhardt
Klaus
K
Department of Obstetrics and Gynaecology, School of Medicine, J.W. Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany. strebhardt@em.uni-frankfurt.de
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; D000097868:Polo-like Kinases
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C486256:PLK3 protein, human; D000097868:Polo-like Kinases; C490219:PLK4 protein, human; C496126:PLK2 protein, human