Polycomb genes and cancer: Time for clinical application?

被引：58

作者：

Crea, Francesco ^{[1
]}

Paolicchi, Elisa ^{[1
]}

Marquez, Victor E. ^{[2
]}

Danesi, Romano ^{[1
]}

机构：

[1] Univ Pisa, Div Pharmacol, Dept Internal Med, I-56100 Pisa, Italy

[2] NCI, Chem Biol Lab, Frederick, MD 21701 USA

来源：

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY | 2012年 / 83卷 / 02期

关键词：

Polycomb; Cancer stem cell; EZH2; BMI1; DZNeP; TUMOR-CELL PROLIFERATION; STEM-CELL; BREAST-CANCER; PROSTATE-CANCER; INCREASED EXPRESSION; GROUP PROTEINS; PHARMACOLOGICAL DISRUPTION; BMI-1; EXPRESSION; DNA METHYLATION; EZH2;

D O I：

10.1016/j.critrevonc.2011.10.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：184 / 193

页数：10

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