Oncotarget

Research Perspectives:

Polo Like Kinase 2 Tumour Suppressor and cancer biomarker: new perspectives on drug sensitivity/resistance in cancer

Helen M. Coley _, Eleftheria Hatzmichael, Sarah P. Blagden, Iain A. McNeish, Alastair Thompson, Tim Crook and Nelofer Syed

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Oncotarget. 2012; 3:78-83. https://doi.org/10.18632/oncotarget.332

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Abstract

Helen M. Coley1, Eleftheria Hatzimichael2, Sarah Blagden3, Iain McNeish4, Alastair Thompson5, Tim Crook5 and Nelofer Syed6

1 Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK

2 Department of Hematology, University Hospital of Ioannina, Ioannina, Greece

3 Department of Medical Oncology, Hammersmith Hospital, London, W12 0HU, UK

4 Department of Medical Oncology, St Bartholomew’s Hospital, London, EC1, UK

5 Dundee Cancer Centre, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK

6 Neuro-Oncology Research Group, Charing Cross Hospital, Imperial College, London, W6 8RF, UK

Received: September 15, 2011; Accepted: January 26, 2012; Published: January 28, 2012;

Keywords: Polo Like Kinases, Chemotherapy resistance, collateral sensitivity

Correspondence:

Helen M. Coley, email:

Abstract

The polo-like kinase PLK2 has recently been identified as a potential theranostic marker in the management of chemotherapy sensitive cancers. The methylation status of the PLK2 CpG island varies with sensitivity to paclitaxel and platinum in ovarian cancer cell lines. Importantly, extrapolation of these in vitro data to the clinical setting confirms that the methylation status of the PLK2 CpG island predicts outcomes in patients treated with carboplatin & paclitaxel chemotherapy. A second cell cycle regulator, p57Kip2, is also subject to epigenetic silencing in carboplatin resistance in vitro and in vivo, emphasising that cell cycle regulators are important determinants of sensitivity to chemotherapeutic agents and providing insights into the phenomenon of collateral drug sensitivity in oncology. Understanding the mechanistic basis and identification of robust biomarkers to predict collateral sensitivity may inform optimal use of chemotherapy in patients receiving multiple lines of treatment.


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