Bladder cancer in the most advanced, muscle-invasive stage is lethal, and very limited therapeutic advances have been reported for decades. To date, cisplatin-based chemotherapy remains the first-line therapy for advanced bladder cancer. Late-line options have historically been limited. In the past few years, next-generation sequencing technology has enabled chromatin remodelling gene mutations to be characterized, showing that these alterations are more frequent in urothelial bladder carcinoma than in other cancer types. Histone modifiers have functional roles in tumour progression by modulating the expression of tumour suppressors and oncogenes and, therefore, have been considered as novel drug targets for cancer therapy. The roles of epigenetic reprogramming through histone modifications have been increasingly studied in bladder cancer, and the therapeutic efficacy of targeting those histone modifiers genetically or chemically is being assessed in preclinical studies. Results from preclinical studies in bladder cancer encouraged the investigation of some of these drugs in clinical trials, which yield mixed results. Further understanding of how alterations of histone modification mechanistically contribute to bladder cancer progression, drug resistance and tumour microenvironment remodelling will be required to facilitate clinical application of epigenetic drugs in bladder cancer.

处于最晚期、肌肉浸润阶段的膀胱癌是致命的，几十年来报道的治疗进展非常有限。迄今为止，基于顺铂的化疗仍然是晚期膀胱癌的一线治疗方法。晚线选择历来是有限的。在过去的几年中，新一代测序技术已经能够对染色质重塑基因突变进行表征，表明这些改变在膀胱尿路上皮癌中比其他癌症类型中更常见。组蛋白修饰剂通过调节肿瘤抑制因子和癌基因的表达在肿瘤进展中发挥功能性作用，因此被认为是癌症治疗的新药物靶点。通过组蛋白修饰进行表观遗传重编程的作用在膀胱癌中得到了越来越多的研究，并且在临床前研究中正在评估以遗传或化学方式靶向这些组蛋白修饰剂的治疗效果。膀胱癌临床前研究的结果鼓励了对其中一些药物进行临床试验的研究，但结果好坏参半。需要进一步了解组蛋白修饰的改变如何在机制上促进膀胱癌进展、耐药性和肿瘤微环境重塑，以促进表观遗传药物在膀胱癌中的临床应用。