Aurora kinases: new targets for cancer therapy.
The Aurora kinase family is a collection of highly related serine/threonine kinases that functions as a key regulator of mitosis. In mammalian cells, Aurora has evolved into three related kinases known as Aurora-A, Aurora-B, and Aurora-C. These kinases are overexpressed in a number of human cancers, and transfection studies have established Aurora-A as a bone fide oncogene. Because Aurora overexpression is associated with malignancy, these kinases have been targeted for cancer therapy. This article reviews the multiple functions of Aurora kinase in the regulation of mitosis and the mitotic checkpoint, the role of abnormal Aurora kinase activity in the development of cancer, the putative mechanisms of Aurora kinase inhibition and its antitumor effects, the development of the first generation of Aurora kinase inhibitors, and prospects for the future of Aurora kinase inhibition in the treatment of cancer.
Carvajal
Richard D
RD
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Tse
Archie
A
Schwartz
Gary K
GK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C576921:AURKB protein, human; C576927:AURKC protein, human; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases