Targeting Aurora kinases in ovarian cancer.
Although recurrent epithelial ovarian cancer initially responds well to current first-line adjuvant therapy, eventually the disease becomes resistant to chemotherapy. Novel strategies are needed to reverse chemoresistance in order to treat relapsed ovarian cancer effectively. One strategy is to target aberrant expression activation of Aurora kinases that are essential for the regulation of chromosome segregation and cytokinesis during mitosis and which play a role in tumourigenesis and progression in a wide range of human tumours, including ovarian cancer. The purpose of this article is to review Aurora kinases and their inhibitors in human epithelial ovarian cancer as an impetus to the development of effective and less toxic regimens for ovarian cancer. In addition, this review tries to define the differences between cytotoxic chemotherapeutic agents and molecular therapeutic agents: both groups of agents have either a single specific target or multiple specific targets, while their differences lie in their toxicity profiles and the way to determine their dosages for further studies. The authors propose that Aurora kinase inhibitors be developed as molecular therapeutic agents in order to minimise their toxicities and maximise their antitumour activities for ovarian cancer treatment.
Fu
Siqing
S
Department of Gynecologic Medical Oncology, The University of Texas, MD Anderson Cancer Center, PO Box 301439, Houston, Texas 77230-1439, USA. siqingfu@mdanderson.org
Hu
Wei
W
Kavanagh
John J
JJ
Bast
Robert C
RC
D000818:Animals; D064127:Aurora Kinases; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000201:enzymology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases