Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Cancer Center, Zhejiang University, Hangzhou 310058, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
Drug Discov Today. 2023 Jun;28(6):103584. doi: 10.1016/j.drudis.2023.103584. Epub 2023 Apr 13.
Oncofusion proteins drive the development of about 16.5% of human cancers, functioning as the unique pathogenic factor in some cancers. The targeting of oncofusion proteins is an attractive strategy to treat malignant tumors. Recently, triggering the degradation of oncofusion proteins has been shown to hold great promise as a therapeutic strategy. Here, we review the recent findings on the mechanisms that maintain the high stability of oncofusion proteins. Then, we summarize strategies to target the degradation of oncofusion proteins through the ubiquitin-proteasome pathway, the autophagy-lysosomal pathway, and the caspase-dependent pathway. By examining oncofusion protein degradation in cancer, we not only gain better insight into the carcinogenic mechanisms that involve oncofusion proteins, but also raise the possibility of treating oncofusion-driven cancer.
癌融合蛋白驱动约 16.5%的人类癌症的发展，作为某些癌症中独特的致病因素发挥作用。针对癌融合蛋白是治疗恶性肿瘤的一种有吸引力的策略。最近，已经表明触发癌融合蛋白的降解具有作为治疗策略的巨大潜力。在这里，我们回顾了维持癌融合蛋白高稳定性的机制的最新发现。然后，我们总结了通过泛素-蛋白酶体途径、自噬溶酶体途径和 caspase 依赖性途径靶向癌融合蛋白降解的策略。通过研究癌融合蛋白在癌症中的降解，我们不仅更好地了解涉及癌融合蛋白的致癌机制，而且还为治疗癌融合蛋白驱动的癌症提供了可能性。
