title: Polo Like Kinase 2 Tumour Suppressor and cancer biomarker: new perspectives on drug sensitivity/resistance in ovarian cancer.
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 and 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.
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK. h.coley@surrey.ac.uk
authors.forename: Helen M
authors.initials: HM
authors.lastname: Coley
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Hatzimichael
authors.forename: Sarah
authors.initials: S
authors.lastname: Blagden
authors.forename: Iain
authors.initials: I
authors.lastname: McNeish
authors.forename: Alastair
authors.initials: A
authors.lastname: Thompson
authors.forename: Tim
authors.initials: T
authors.lastname: Crook
authors.forename: Nelofer
authors.initials: N
authors.lastname: Syed
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases