Targeting Cyclin-Dependent Kinases in Ovarian Cancer

Abstract

Ovarian cancer is the most common gynecological malignancy in the United States, and prognosis is generally poor because the disease is often diagnosed at an advanced stage. Cyclin-dependent kinases (CDKs) are a family of serine/threonine kinases whose activity is regulated by CDK inhibitors (CKIs) and cyclins. Generally, cyclins and CKIs promote and inhibit CDK activation, respectively. Since cancer commonly involves dysregulation of cell cycle, cyclins and CDKs have been targeted in a variety of tumors using small molecules, peptides, immunotherapy, and CKIs. In this review we discuss the significance of cell cycle dysregulation in ovarian cancer as well as recent advances targeting CDKs in ovarian cancer and potential future directions. Although many of the studies assessing CDK-targeting therapies in ovarian cancer are at an early preclinical stage, there is significant evidence that targeting CDKs, particularly in combination with traditional platinum-based drugs, could have significant efficacy in ovarian cancer. Nevertheless, before these agents can be investigated in humans, additional preclinical development is needed, including using in vivo tumor models and additional studies into their mechanism of action.

Keywords: Cyclin-Dependent Kinases; Gynecological Malignancy; Ovarian Cancer.