This Article Full Text (PDF) All Versions of this Article: theoncologist.2009-0010v1 14/6/559    most recent eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Google Scholar Articles by Schöffski, P. PubMed PubMed Citation Articles by Schöffski, P.

Polo-Like Kinase (PLK) Inhibitors in Preclinical and Early Clinical Development in Oncology

Department of General Medical Oncology, Leuven Cancer Institute, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium

Key Words. Polo-like kinase • PLK • Polo • Serine/threonine kinase

Correspondence: Correspondence: Patrick Schöffski, M.D., M.P.H., Department of General Medical Oncology, Leuven Cancer Institute, University Hospital Gasthuisberg, Catholic University Leuven, Herestraat 49, 3000 Leuven, Belgium. Telephone: 32-16-34-69-00; Fax: 32-16-34-69-01; e-mail: patrick.schoffski{at}uz.kuleuven.be

Received January 21, 2009; accepted for publication April 30, 2009.

The article discusses unlabeled, investigational, or alternative use(s) of a product, device or technique: review of novel drugs from several manufacturers for a novel target (Polo).

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Polo-like kinases (PLKs) are a group of highly conserved serine/threonine protein kinases that play a key role in processes such as cell division and checkpoint regulation of mitosis. About 80% of human tumors, of various origins, express high levels of PLK transcripts. However, PLK mRNA is mostly absent in surrounding healthy tissues. Overexpression of PLK is associated with a poor prognosis in several tumor types and a lower overall survival rate. The overexpression of PLKs in human tumors, but not in healthy nondividing cells, makes them an attractive, selective target for cancer drug development. PLK inhibitors interfere with different stages of mitosis, such as centrosome maturation, spindle formation, chromosome separation, and cytokinesis. They induce mitotic chaos and severely perturb cell cycle progression, eventually leading to cancer cell death. Several PLK inhibitors are in development and are undergoing evaluations as potential cancer treatments. This review includes an overview of PLK inhibitors in early clinical development (i.e., BI 2536, BI 6727, GSK461364, ON 019190.Na, and HMN-214) and in advanced preclinical development (i.e., ZK-thiazolidinone, NMS-1, CYC-800, DAP-81, and LC-445). If proof of principle is confirmed in large studies, PLK inhibitors will offer a new targeted antitumor therapy for cancer patients.