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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
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