Title:Mitotic Kinase Inhibitors as Therapeutic Interventions for Prostate Cancer:
Evidence from In Vitro Studies
Volume: 23
Issue: 14
Author(s): Aadil Javed, Gülseren Özduman, Sevda Altun, Doğan Duran, Dilan Yerli, Tilbe Özar, Faruk Şimşek and Kemal Sami Korkmaz*
Affiliation:
- Department of Bioengineering, Faculty of Engineering, Cancer Biology Laboratory, Ege University, Bornova, Izmir, Turkey
Keywords:
Prostate, cancer, mitosis, kinases, inhibitors, cell cycle, cell lines.
Abstract: Prostate cancer is one of the devastating diseases characterized by genetic changes leading
to uncontrolled growth and metastasis of the cells of the prostate gland and affects men worldwide.
Conventional hormonal and chemotherapeutic agents are effective in mitigating the disease if diagnosed
at an early stage. All dividing eukaryotic cells require mitotic progression for the maintenance of
genomic integrity in progeny populations. The protein kinases, upon activation and de-activation in an
ordered fashion, lead to spatial and temporal regulation of the cell division process. The entry into
mitosis along with the progression into sub-phases of mitosis is ensured due to the activity of mitotic
kinases. These kinases include Polo-Like-Kinase 1 (PLK1), Aurora kinases, and Cyclin-Dependent-
Kinase 1 (CDK1), among others. The mitotic kinases, among others, are usually overexpressed in many
cancers and can be targeted using small molecule inhibitors to reduce the effects of these regulators on
mechanisms, such as regulation of genomic integrity and mitotic fidelity. In this review, we attempted
to discuss the appropriate functions of mitotic kinases revealed through cell culture studies and the
impact of their respective inhibitors derived in pre-clinical studies. The review is designed to elucidate
the growing field of small molecule inhibitors and their functional screening or mode of action at the
cellular and molecular level in the context of Prostate Cancer. Therefore, studies performed specifically
on cells of Prostatic-origin are narrated in this review, culminating in a comprehensive view of the
specific field of mitotic kinases that can be targeted for therapy of Prostate cancer.
