Hosea Rendy, Hillary Sharon, Wu Shourong, Kasim Vivi
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China.
Cancers (Basel). 2023 Jul 5;15(13):3506. doi: 10.3390/cancers15133506.
Cancer represents a significant and persistent global health burden, with its impact underscored by its prevalence and devastating consequences. Whereas numerous oncogenes could contribute to cancer development, a group of transcription factors (TFs) are overactive in the majority of tumors. Targeting these TFs may also combat the downstream oncogenes activated by the TFs, making them attractive potential targets for effective antitumor therapeutic strategy. One such TF is yin yang 1 (YY1), which plays crucial roles in the development and progression of various tumors. In preclinical studies, YY1 inhibition has shown efficacy in inhibiting tumor growth, promoting apoptosis, and sensitizing tumor cells to chemotherapy. Recent studies have also revealed the potential of combining YY1 inhibition with immunotherapy for enhanced antitumor effects. However, clinical translation of YY1-targeted therapy still faces challenges in drug specificity and delivery. This review provides an overview of YY1 biology, its role in tumor development and progression, as well as the strategies explored for YY1-targeted therapy, with a focus on their clinical implications, including those using small molecule inhibitors, RNA interference, and gene editing techniques. Finally, we discuss the challenges and current limitations of targeting YY1 and the need for further research in this area.
癌症是一项重大且持续存在的全球健康负担，其普遍性和毁灭性后果凸显了它的影响。尽管众多癌基因可能促成癌症发展，但一组转录因子（TFs）在大多数肿瘤中过度活跃。靶向这些转录因子也可能对抗由它们激活的下游癌基因，使其成为有效抗肿瘤治疗策略中有吸引力的潜在靶点。阴阳1（YY1）就是这样一种转录因子，它在各种肿瘤的发生和发展中起关键作用。在临床前研究中，抑制YY1已显示出在抑制肿瘤生长、促进细胞凋亡以及使肿瘤细胞对化疗敏感方面的疗效。最近的研究还揭示了将抑制YY1与免疫疗法相结合以增强抗肿瘤效果的潜力。然而，YY1靶向治疗的临床转化在药物特异性和递送方面仍面临挑战。本综述概述了YY1的生物学特性、其在肿瘤发生和发展中的作用，以及针对YY1靶向治疗所探索的策略，重点关注其临床意义，包括使用小分子抑制剂、RNA干扰和基因编辑技术的策略。最后，我们讨论了靶向YY1的挑战和当前局限性以及该领域进一步研究的必要性。
