突变P53功能研究新进展与个性化的肿瘤治疗新策略

Recent advances in mutant p53 and novel personalized strategies for cancer therapy

p53是迄今为止研究最多的一种抑癌蛋白,最新研究仍在不断地揭示p53在调控机体代谢、生殖方面的新功能。同时,也揭示了不同p53突变蛋白的获得性新功能在肿瘤发生中的促进作用。这些研究对于了解p53突变的个性化新功能,寻找再激活野生型p53,校正突变p53的新途径奠定了基础,不同突变p53蛋白的个性化治疗将是未来肿瘤治疗的热点。文章综述了已发现的一些突变p53的获得性新功能,及针对不同的p53功能缺陷进行的p53蛋白功能再激活的策略:通过小分子或多肽再激活肿瘤细胞中的p53突变蛋白的野生型功能;通过重组的腺病毒在肿瘤细胞中表达野生型p53蛋白;通过抑制MDM2与p53的相互作用稳定野生型p53蛋白。对p53不同位点突变的深入研究可以帮助我们制定更合理的个性化治疗方案,寻求更有效的肿瘤治疗新途径。

Protein p53 is the most intensively studied tumor suppressor protein.Recent studies keep revealing its new function in metabolism and reproduction.At the same time,it is also found that varieties of p53 mutant gained new function in promoting tumorigenesis.These studies provide the basis for understanding the personalized gain of function of p53 mu-tants and help us searching for the new strategies for reactivation of wild-type p53 and correction of the function of p53 mutants.The personalized treatment targeting different p53 mutants will be the focus for cancer treatment.Here,we re-viewed the discovered gain of function of some p53 mutants and the molecular strategies for reactivating wild type p53 function： by use of small molecules or polypeptides to reactivate the wild type function of p53 mutants in tumor cells;by exogenous expression of wild type p53 carried by recombinant adenovirus in tumor cells;and by inhibition the interaction between p53 and mdm2 to stabilize wild type p53 proteins.Further study of variety of p53 point mutations farcilitates de-signing more effectively personalized strategies in the cancer therapy.