Epigenetic drug discovery field has evidenced significant advancement in the recent times. A plethora of small molecule inhibitors have progressed to clinical stage investigations and are being explored exhaustively to ascertain conclusive benefits in diverse malignancies. Literature precedents indicates that substantial amount of efforts were directed towards the use of epigenetic tools in monotherapy as well as in combination regimens at the clinical level, however, the preclinical/preliminary explorations were inclined towards the identification of prudent approaches that can leverage the anticancer potential of small molecule epigenetic inhibitors as single agents only. This review article presents an update of FDA approved epigenetic drugs along with the epigenetic inhibitors undergoing clinical stage investigations in different cancer types. A detailed discussion of the pragmatic strategies that are expected to steer the progress of the epigenetic therapy through the implementation of emerging approaches such as PROTACS and CRISPR/Cas9 along with logical ways for scaffold fabrication to selectively approach the enzyme isoforms in pursuit of garnering amplified antitumor effects has been covered. In addition, the compilation also presents the rational strategies for the construction of multi-targeting scaffold assemblages employing previously identified pharmacophores as potential alternatives to the combination therapy.

中文翻译：

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表观遗传癌症治疗的最新进展：临床进展和新兴趋势

表观遗传学药物发现领域近年来取得了重大进展。大量的小分子抑制剂已进入临床阶段研究，并正在进行详尽的探索，以确定对多种恶性肿瘤确实的益处。文献先例表明，大量的努力是针对在临床水平的单一疗法以及联合治疗方案中使用表观遗传学工具，然而，临床前/初步探索倾向于确定可以利用抗癌潜力的审慎方法小分子表观遗传抑制剂仅作为单一药物。这篇综述文章介绍了 FDA 批准的表观遗传药物以及在不同癌症类型中正在进行临床阶段研究的表观遗传抑制剂的最新情况。详细讨论了实用策略，这些策略预计通过实施 PROTACS 和 CRISPR/Cas9 等新兴方法来引导表观遗传治疗的进展，以及支架制造的逻辑方法，以选择性地处理酶异构体，以追求获得放大的抗肿瘤效果影响已被覆盖。此外，该汇编还提出了利用先前确定的药效团作为联合疗法的潜在替代方案构建多靶点支架组合的合理策略。