Foghorn Therapeutics, Inc, Cambridge, MA 02142, USA.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02215, USA.
Trends Genet. 2020 Dec;36(12):936-950. doi: 10.1016/j.tig.2020.07.011. Epub 2020 Aug 29.
Small molecule-based targeting of chromatin regulatory factors has emerged as a promising therapeutic strategy in recent years. The development and ongoing clinical evaluation of novel agents targeting a range of chromatin regulatory processes, including DNA or histone modifiers, histone readers, and chromatin regulatory protein complexes, has inspired the field to identify and act upon the full compendium of therapeutic opportunities. Emerging studies highlight the frequent involvement of altered mammalian Switch/Sucrose-Nonfermentable (mSWI/SNF) chromatin-remodeling complexes (also called BAF complexes) in both human cancer and neurological disorders, suggesting new mechanisms and accompanying routes toward therapeutic intervention. Here, we review current approaches for direct targeting of mSWI/SNF complex structure and function and discuss settings in which aberrant mSWI/SNF biology is implicated in oncology and other diseases.
近年来，基于小分子的染色质调节因子靶向治疗策略已经兴起。新型药物的开发和不断的临床评估针对一系列染色质调节过程，包括 DNA 或组蛋白修饰剂、组蛋白读取器和染色质调节蛋白复合物，激发了该领域识别和利用全部治疗机会的热情。新兴研究强调了改变的哺乳动物转换/蔗糖非发酵（mSWI/SNF）染色质重塑复合物（也称为 BAF 复合物）在人类癌症和神经紊乱中的频繁参与，提示了新的机制和伴随的治疗干预途径。在这里，我们回顾了直接靶向 mSWI/SNF 复合物结构和功能的当前方法，并讨论了异常的 mSWI/SNF 生物学在肿瘤学和其他疾病中的涉及情况。
