Bromodomains are protein-protein interaction modules with a great diversity in terms of number of proteins and their function. The bromodomain and extraterminal protein (BET) represents a distinct subclass of bromodomain proteins mainly involved in transcriptional regulation via their interaction with acetylated chromatin. In cancer cells BET proteins are found to be altered in many ways such as overexpression, mutations and fusions of BET proteins or their interference with cancer relevant signaling pathways and transcriptional programs in order to sustain cancer growth and viability. Blocking BET protein function with small molecules is associated with therapeutic activity. Consequently, a variety of small molecules have been developed and a number of phase I clinical trials have explored their tolerability and efficacy in patients with solid tumors and hematological malignancies. We will review the rational for applying BET inhibitors in the clinic and we will discuss the toxicity profile as well as efficacy of this new class of protein inhibitors. We will also highlight the emerging problem of treatment resistance and the potential these drugs might have when combined with other anti-cancer therapies.

中文翻译：

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充分利用BET：BET抑制剂在恶性肿瘤治疗中的新兴作用。

溴结构域是蛋白质-蛋白质相互作用模块，在蛋白质数量及其功能方面具有很大的差异。溴结构域和末端外蛋白（BET）代表了溴结构域蛋白的独特亚类，主要通过它们与乙酰化染色质的相互作用而参与转录调控。在癌细胞中，发现BET蛋白会以多种方式发生改变，例如BET蛋白的过表达，突变和融合，或它们与癌症相关的信号传导途径和转录程序的干扰，以维持癌症的生长和生存。用小分子阻断BET蛋白的功能与治疗活性有关。所以，已经开发了多种小分子，并且许多I期临床试验已经探索了它们在实体瘤和血液系统恶性肿瘤患者中的耐受性和疗效。我们将审查在临床上应用BET抑制剂的合理性，并将讨论这种新型蛋白抑制剂的毒性特征和功效。我们还将重点介绍新出现的治疗耐药性问题以及这些药物与其他抗癌疗法联合使用时可能具有的潜力。