Polo‑like Kinase 1 as a Target for Anti‑tumor Therapy


Authors: I. Procházková;  B. Vojtěšek
Authors‘ workplace: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in: Klin Onkol 2015; 28(Supplementum 2): 32-39
doi: 10.14735/amko20152S32

Overview

Individual proteins from polo-like kinase (Plk) family fulfil different but critical functions in regulating cell cycle and coordinate cell response to DNA  damage. The most studied one from this five  member family is Plk1. It is a serine/ threonine kinase that plays a pivotal role in many aspects of mitosis and its deregulation is common in various tumor types where the elevated level is mostly associated with worse prognosis. From the therapeutical point of view, intertwin­ed relationship between Plk1 and p53 protein is very interesting and will be discussed. Not only for these reasons, Plk1 has become an attractive target for anti‑tumor drug development. The most promising seems to be ATP binding site inhibitor Volasertib (BI 6727) which provided a survival benefit for patients with acute myeloid leukemia and is now tested in phase III clinical trial. A new generation of Plk1 inhibitors that target the second druggable domain of Plk1, the polo- box domain, is currently being tested preclinically and are believed to improve Plk1 specificity.

Key words:
polo like kinase 1 –  tumor suppressor protein p53 –  ATP  competitive inhibitors –  polo- box domain –  drug evaluation studies

This study was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101), MEYS – NPS I – LO1413, MH CZ – DRO (MMCI, 00209805) and BBMRI_CZ (LM2010004).

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
9. 4. 2015

Accepted:
19. 6. 2015


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