Yu Chunyu, Sun Jie, Tong Jinlong, Xu Ziqing, Zhang Qijia
School of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, NHC Key Laboratory of Bbiotechnology Ddrugs (Shandong Academy of Medical Sciences), Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Jinan, 250117, Shandong, China.
Department No. 1 of Oncology, The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine, No. 1-1 Zhongfu Road, Gulou District, Nanjing, 210000, Jiangsu Province,, People's Republic of China.
Invest New Drugs. 2025 Jun 13. doi: 10.1007/s10637-025-01555-2.
The dysregulation of cellular epigenetic machinery has been established as a fundamental driver of oncogenesis. This recognition has propelled cancer epigenetics to the forefront of biomedical research, particularly regarding the mechanistic characterization of epigenetic switching events. These molecular switches represent critical regulatory nodes in the malignant transformation. The epigenetic switch is a complex structure formed through interactions between nucleic acid-protein complexes or protein-protein interaction complexes and specific DNA fragments. Triggered by a priming event, this molecular apparatus can reversibly activate or repress the transcription of multiple downstream genes. The inherent reversibility of these epigenetic switches presents novel therapeutic opportunities for targeted cancer intervention. Consequently, this review provides a systematic analysis of cancer-associated epigenetic switches identified in the past decade.
细胞表观遗传机制的失调已被确认为肿瘤发生的一个基本驱动因素。这一认识推动癌症表观遗传学成为生物医学研究的前沿领域,特别是在表观遗传转换事件的机制表征方面。这些分子开关代表了恶性转化中的关键调控节点。表观遗传开关是通过核酸 - 蛋白质复合物或蛋白质 - 蛋白质相互作用复合物与特定DNA片段之间的相互作用形成的复杂结构。由引发事件触发后,这种分子装置可以可逆地激活或抑制多个下游基因的转录。这些表观遗传开关的固有可逆性为靶向癌症干预提供了新的治疗机会。因此,本综述对过去十年中发现的与癌症相关的表观遗传开关进行了系统分析。