Marques-Magalhães Ângela, Graça Inês, Henrique Rui, Jerónimo Carmen
Cancer Biology and Epigenetics Group - Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal.
Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal.
Front Pharmacol. 2018 Apr 13;9:366. doi: 10.3389/fphar.2018.00366. eCollection 2018.
Urological cancers are a heterogeneous group of malignancies accounting for a considerable proportion of cancer-related morbidity and mortality worldwide. Aberrant epigenetic traits, especially altered DNA methylation patterns constitute a hallmark of these tumors. Nonetheless, these alterations are reversible, and several efforts have been carried out to design and test several epigenetic compounds that might reprogram tumor cell phenotype back to a normal state. Indeed, several DNMT inhibitors are currently under evaluation for therapeutic efficacy in clinical trials. This review highlights the critical role of DNA methylation in urological cancers and summarizes the available data on pre-clinical assays and clinical trials with DNMT inhibitors in bladder, kidney, prostate, and testicular germ cell cancers.
泌尿系统癌症是一组异质性恶性肿瘤,在全球范围内,其在癌症相关的发病率和死亡率中占相当大的比例。异常的表观遗传特征,尤其是DNA甲基化模式的改变,是这些肿瘤的一个标志。尽管如此,这些改变是可逆的,并且已经开展了多项工作来设计和测试几种可能将肿瘤细胞表型重新编程回正常状态的表观遗传化合物。事实上,目前有几种DNA甲基转移酶(DNMT)抑制剂正在临床试验中评估其治疗效果。这篇综述强调了DNA甲基化在泌尿系统癌症中的关键作用,并总结了关于DNMT抑制剂在膀胱癌、肾癌、前列腺癌和睾丸生殖细胞癌的临床前试验和临床试验的现有数据。