Epigenetic therapy in urologic cancers: an update on clinical trials.
Epigenetic therapy in urologic cancers: an update on clinical trials.
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DOI：
10.18632/oncotarget.14226
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发表时间：
2017-02-14
期刊：
影响因子：
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通讯作者：
Castelo-Branco P
中科院分区：
文献类型：
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作者：
Faleiro I;Leão R;Binnie A;de Mello RA;Maia AT;Castelo-Branco P
表观遗传失调是导致癌症发展和进展的许多因素之一。在泌尿系统癌症中已经鉴定出许多表观遗传改变，包括组蛋白修饰、DNA甲基化改变和microRNA表达。由于这些变化是可逆的，因此正在努力开发恢复细胞正常表观遗传模式的表观遗传药物，并且已经进行了许多临床试验以测试其临床潜力。在这篇综述中，我们分析了多个临床试验（n=51），测试这些药物在泌尿系统癌症患者的疗效。最常用的表观遗传药物是组蛋白去乙酰化酶抑制剂，其次是反义寡核苷酸、DNA甲基转移酶抑制剂和组蛋白去甲基化酶抑制剂，最后一种仅在前列腺癌中进行测试。在超过50%的临床试验中，表观遗传药物被用作联合治疗的一部分，取得了最佳效果。某些癌症的表观遗传调控仍然是研究的问题，但无疑将为个性化医疗时代的新治疗方法打开一扇窗户。泌尿系统恶性肿瘤的治疗的未来可能包括多药方案，其中表观遗传修饰药物将发挥重要作用。
Epigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clinical trials are already underway to test their clinical potential. In this review we analyze multiple clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers. The most frequently used epigenetic drugs were histone deacetylase inhibitors followed by antisense oligonucleotides, DNA methyltransferase inhibitors and histone demethylase inhibitors, the last of which are only being tested in prostate cancer. In more than 50% of the clinical trials considered, epigenetic drugs were used as part of combination therapy, which achieved the best results. The epigenetic regulation of some cancers is still matter of research but will undoubtedly open a window to new therapeutic approaches in the era of personalized medicine. The future of therapy for urological malignancies is likely to include multidrug regimens in which epigenetic modifying drugs will play an important role.