EZH2 as a mediator of treatment resistance in melanoma

被引：22
作者：
Tiffen, Jessamy C. [1 ]
Gallagher, Stuart J. [1 ]
Tseng, Hsin-Yi [1 ]
Filipp, Fabian V. [2 ]
Fazekas de St Groth, Barbara [3 ]
Hersey, Peter [1 ]
机构：
[1] Univ Sydney, Centenary Inst, Melanoma Immunol & Oncol Grp, Camperdown, NSW, Australia
[2] Univ Calif Merced, Program Quantitat Syst Biol, Syst Biol & Canc Metab, Merced, CA USA
[3] Univ Sydney, Centenary Inst, Cell Biol Program T, Camperdown, NSW, Australia
来源：
PIGMENT CELL & MELANOMA RESEARCH | 2016年 / 29卷 / 05期
基金：
英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词：
melanoma; enhancer of zeste homolog 2; epigenetic; immune suppression; treatment resistance;
D O I：
10.1111/pcmr.12481
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Direct treatments of cancer such as chemotherapy, radiotherapy and targeted therapy have been shown to depend on recruitment of the immune system for their effectiveness. Recent studies have shown that development of resistance to direct therapies such as BRAF inhibitors in melanoma is associated with suppression of immune responses. We point to emerging data that implicate activation of the polycomb repressive complex 2 (PRC2) and its catalytic component-enhancer of zeste homolog 2 (EZH2)-in progression of melanoma and suppression of immune responses. EZH2 appears to have an important role in differentiation of CD4 T cells and particularly in the function of T regulatory cells, which suppress immune responses to melanoma. Wereview mechanisms of EZH2 activation at the genomic level and from activation of the MAP kinase, E2F or NF-kB2 pathways. These studies are consistent with activation of EZH2 as a common mechanism for induction of immune suppression in patients failing direct therapies and suggest EZH2 inhibitors may have a role in combination with immunotherapy and targeted therapies to prevent development of immunosuppression.
引用
收藏
页码：500 / 507
页数：8
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