靶向p53的抗肿瘤药物研究进展

Research advances in the antitumor drugs targeting p53

编码蛋白P53(肿瘤蛋白53,TP53)的基因具有控制细胞周期、细胞凋亡及控制新生血管形成等功能。该基因的突变发生于>50%癌症患者中,在一些特定的肿瘤细胞亚型中,该基因突变频率尤高。p53基因突变能明显促进恶性肿瘤的发生发展,从而显著增加患癌风险,因此,p53已成为癌症研究中一个很有吸引力的药物靶点。针对p53基因突变的药物研究主要有两方面:直接作用于突变型p53基因(恢复p53野生型活性及诱导突变型P53蛋白的降解);间接作用于突变型P53蛋白。本文主要讨论p53的研究现状,靶向p53的抗肿瘤药物研究进展及面临的困难。

The TP53 gene,encoding p53 protein,exerts very important functions,including the regulation of cell cycle,apoptosis and new blood vessel formation Mutations on this gene occur in over 50% of cancer patients,with particularly higher frequency in some specific tumor subtypes. The p53 mutation could evidently promote the occurrence and development of malignant tumors and thus markedly increase the risk of cancer. Therefore,p53 has been an important target for antitumor drugs. Researches on the p53-targeting drugs have been focusing on two directions of their effects：the direct effects on the p53 mutations to restore wild-type p53 activity and degrade mutated p53 proteins and the indirect effects on the p53 mutations. This paper reviews the current research status of p53,the research progress in the p53-targeted antitumor drugs,as well as the problems from related studies.