Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy.
Immunotherapy. 2013 Oct;5(10):1103-16. doi: 10.2217/imt.13.108.
Malignant melanoma is a complex disease that arises and evolves due to a myriad of genetic and epigenetic events. Among these, the interaction between epigenetic alterations (i.e., histone modifications, DNA methylation, mRNA silencing by miRNAs and nucleosome repositioning) has been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, DNA repair, apoptosis, invasion and immune recognition. Differently to genetic lesions, epigenetic changes are potentially pharmacologically reversible by using epigenetic drugs. Along this line, preclinical and clinical findings indicate that these drugs, given alone or in combination therapies, can efficiently modulate the immunophenotype of melanoma cells. The aim of this review is to provide a comprehensive summary of melanoma epigenetics and the current use of epigenetic drugs in the clinical setting.
恶性黑色素瘤是一种复杂的疾病，由于众多的遗传和表观遗传事件而产生和演变。在这些事件中，表观遗传改变（即组蛋白修饰、DNA 甲基化、miRNA 介导的 mRNA 沉默和核小体重定位）之间的相互作用最近被确定为通过影响关键的细胞途径（如细胞周期调控、DNA 修复、细胞凋亡、侵袭和免疫识别）在黑色素瘤的发生和进展中发挥重要作用。与遗传损伤不同，表观遗传变化可以通过使用表观遗传药物在药理学上具有潜在的可逆性。沿着这条线，临床前和临床研究结果表明，这些药物单独或联合治疗，可以有效地调节黑色素瘤细胞的免疫表型。本综述的目的是全面总结黑色素瘤的表观遗传学和目前在临床环境中使用表观遗传药物的情况。
