Epigenetic and genomic alterations regulate the transcriptional landscape of cells during cancer onset and progression. Recent clinical studies targeting the epigenetic ‘readers’ (bromodomains) for cancer therapy have established the effectiveness of bromodomain (BRD) and extraterminal (BET) inhibitors in treating several types of cancer. In this review, we discuss key mechanisms of BET inhibition and synergistic combinations of BET inhibitors with histone deacetylase inhibitors (HDACi), histone methyltransferase inhibitors (HMTi), DNA methyltransferase inhibitors (DNMTi), kinase, B-cell lymphoma 2 (Bcl-2) and proteosome inhibitors, and immunomodulatory drugs for cancer therapy. We also highlight the potential of such combinations to overcome drug resistance, and the evolving approaches to developing novel BET inhibitors.

表观遗传学和基因组学改变可调节癌症发作和进展过程中细胞的转录情况。针对表观遗传“阅读器”（bromodomains）进行癌症治疗的最新临床研究已经确定了bromodomain（BRD）和Extraterminal（BET）抑制剂在治疗几种类型癌症中的有效性。在这篇综述中，我们讨论了BET抑制的关键机制以及BET抑制剂与组蛋白脱乙酰基酶抑制剂（HDACi），组蛋白甲基转移酶抑制剂（HMTi），DNA甲基转移酶抑制剂（DNMTi），激酶，B细胞淋巴瘤2（Bcl-2）的协同组合。 ）和蛋白体抑制剂，以及用于癌症治疗的免疫调节药物。我们还强调了此类组合克服药物耐药性的潜力，以及开发新型BET抑制剂的不断发展的方法。