Driving the degradation of oncofusion proteins for targeted cancer therapy.
Driving the degradation of oncofusion proteins for targeted cancer therapy.
复制标题
DOI：
10.1016/j.drudis.2023.103584
复制
发表时间：
2023-04
影响因子：
7.4
通讯作者：
Xingya Zhang;Ying-qian Chen;Bo Yang;Xuejing Shao;Meidan Ying
中科院分区：
文献类型：
--
作者：
Xingya Zhang;Ying-qian Chen;Bo Yang;Xuejing Shao;Meidan Ying
肿瘤融合蛋白是多种肿瘤发生发展的驱动因子。肿瘤融合蛋白通过逃避降解而表现出极高的稳定性。触发肿瘤融合蛋白降解受到广泛关注。已经阐明了诱导几种肿瘤融合蛋白降解的策略。探索更多的机制和策略是未来的方向。肿瘤融合蛋白驱动了约16.5%的人类癌症的发生，在某些癌症中起着独特的致病因子的作用。肿瘤融合蛋白靶向治疗恶性肿瘤是一个有吸引力的策略。最近，触发肿瘤融合蛋白的降解已被证明是一种很有前途的治疗策略。在这里，我们回顾了最近的研究结果的机制，保持高稳定性的癌融合蛋白。然后，我们总结了通过泛素-蛋白酶体途径、自噬-溶酶体途径和半胱天冬酶依赖途径靶向降解肿瘤融合蛋白的策略。通过研究癌融合蛋白在癌症中的降解，我们不仅可以更好地了解涉及癌融合蛋白的致癌机制，而且还可以提高治疗癌融合驱动的癌症的可能性。
HighlightsOncofusion proteins drive the development of numerous cancers.Oncofusion proteins present extremely high stability by escaping degradation.Triggering the degradation of oncofusion proteins has received extensive attention.Strategies to induce the degradation of several oncofusion proteins have been elucidated.The exploration of more mechanisms and strategies is the way forward.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.