Polo-like kinase 1 inhibitors in mono- and combination therapies: a new strategy for treating malignancies

Abstract

Polo-like kinase 1 (Plk1) inhibitors belong to a new class of drugs for the treatment of malignant diseases. They selectively act against a target (Plk1) which is involved in different stages of mitosis such as centrosome maturation, spindle formation, chromosome separation and cytokinesis. Because Plk1 is mainly expressed in proliferating tissues and overexpressed in cancers, its inhibition is potentially less prone to toxicities associated with current antimitotic agents, which also act on nondividing cells. Several Plk1 inhibitors are being evaluated as cancer treatment drugs. Based on the essential role of Plk1 during mitosis, Plk1 inhibitors target all rapidly dividing cells irrespective of their tumor suppressor or oncogene mutations. In this article, their mechanisms of action, efficacy and toxicity profile are discussed.

Keywords::

• antimitotic agents
• BI 2536, BI 6727 (volasertib)
• GSK461364
• GW843682X
• HMN-214
• NMS-P937 (NMS1286937)
• novel anticancer drugs
• ON 01910.Na
• Polo-like kinase (Plk) inhibitors
• TAK-960
• TKM-080301

Financial & competing interests disclosure

Martin Schuler has received research funding from Boehringer Ingelheim, Novartis and Roche. Martin Schuler has served as compensated consultant to Pfizer, Amgen, Novartis and Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors would like to acknowledge the editorial assistance of Ogilvy Healthworld and GeoMed Global. Boehringer Ingelheim provided financial support for this assistance.