Targeting Aurora kinases in ovarian cancer

Abstract

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.

Keywords::

• Aurora kinases
• Aurora kinase inhibitor
• cell cycle
• chemosensitisation
• mitosis
• molecular therapeutic agent
• ovarian cancer

Acknowledgements

The authors would like to thank Micheal Worley in the Department of Scientific Publications at MD Anderson Cancer Center for editing this manuscript.