以p73为靶点的抗肿瘤药物研究进展

Advances in p73-targeting anti-tumor drugs

肿瘤抑制因子p73可转录形成具有促凋亡(TAp73)和抗凋亡(△Np73)功能的2种亚型。但是,在肿瘤进程中,TAp73-负调节因子(如△Np73、突变p53、MDM2和iASPP)复合体的形成会阻碍TAp73的肿瘤抑制活性。因此,通过靶向抑制负调节因子或破坏TAp73-负调节因子复合体,释放出TAp73,进而达到抑制肿瘤的目的。该文就p73的靶向调控及相关药物的研究进展进行综述。

The transcription factor p73 belongs to the p53 family of tumor suppressors,and can be transcribed into different isoforms with either pro-or anti-apoptotic（ TAp73 and △Np73）functions. However,the tumor suppressor activity of TAp73 is inhibited through complex formation with inhibitory proteins（ e.g. △Np73,mutant p53,MDM2 and iASPP）. Therefore,it is a kind of tumor therapy strategy to reactivate TAp73 through targeting these inhibitors directly or release TAp73 from the complex by targeting their interaction. This review discusses the possible strategies of targeting p73 for its reactivation and the acting mechanism of related compounds.