title: Polycomb genes and cancer: time for clinical application?
abstract: Polycomb group genes (PcGs) are epigenetic effectors, essential for stem cell self-renewal and pluripotency. Two main Polycomb repressive complexes (PRC1, PRC2) mediate gene silencing through histone post-translational modifications. PcGs have been the focus of investigation in cancer research. Many cancer types show an over-expression of PcGs, predicting poor prognosis, metastasis and chemoresistance. Genetic polymorphisms of EZH2 (a PRC2 component) are significantly associated to lung cancer risk. Recently, 3-Deazaneplanocin A (DZNeP) was identified as an efficient inhibitor of PRC2 activity. DZNeP impairs cancer stem cell self-renewal and tumorigenicity. Despite the well-established role of PcGs in cancer stem cell biology, few studies dissected the clinical significance of these genes. In this paper, we explore PcGs as predictive and prognostic factors in oncology, with particular emphasis on what they can add to current biomarkers. We also propose a model for the rational development of DZNeP-based anticancer regimens and suggest the therapeutic applications of this drug.
authors: Department of Internal Medicine, Division of Pharmacology, University of Pisa, Via Roma 55, 56100 Pisa, Italy. fr.crea@gmail.com
authors: Francesco
authors: F
authors: Crea
authors: Elisa
authors: E
authors: Paolicchi
authors: Victor E
authors: VE
authors: Marquez
authors: Romano
authors: R
authors: Danesi
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors; D063146:Polycomb-Group Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D063146:Polycomb-Group Proteins; C048460:3-deazaneplanocin; D063151:Polycomb Repressive Complex 2; D000241:Adenosine