Kamath Divya, Iwakuma Tomoo, Bossmann Stefan H
The University of Kansas Medical Center, Department of Cancer Biology, 3901 Rainbow Blvd, mailstop 1071, 66160 Kansas City, KS, USA.
Children's Mercy Hospital, Adele Hall Campus, 2401 Gillham Rd, Kansas City, MO 64108, USA.
Nanomedicine. 2024 Feb;56:102732. doi: 10.1016/j.nano.2024.102732. Epub 2024 Jan 8.
Among the tumor suppressor genes, TP53 is the most frequently mutated in human cancers, and most mutations are missense mutations causing production of mutant p53 (mutp53) proteins. TP53 mutations not only results in loss of function (LOH) as a transcription factor and a tumor suppressor, but also gain wild-type p53 (WTp53)-independent oncogenic functions that enhance cancer metastasis and progression (Yamamoto and Iwakuma, 2018; Zhang et al., 2022). TP53 has extensively been studied as a therapeutic target as well as for drug development and therapies, however with limited success. Achieving targeted therapies for restoration of WTp53 function and depletion or repair of mutant p53 (mutp53) will have far reaching implication in cancer treatment and therapies. This review briefly discusses the role of p53 mutation in cancer and the therapeutic potential of restoring WTp53 through the advances in mRNA nanomedicine.
在肿瘤抑制基因中，TP53是人类癌症中最常发生突变的基因，大多数突变是错义突变，导致突变型p53（mutp53）蛋白的产生。TP53突变不仅导致作为转录因子和肿瘤抑制因子的功能丧失（LOH），还获得了与野生型p53（WTp53）无关的致癌功能，增强了癌症转移和进展（Yamamoto和Iwakuma，2018年；Zhang等人，2022年）。TP53作为治疗靶点以及药物开发和治疗方法已被广泛研究，但取得的成功有限。实现恢复WTp53功能以及清除或修复突变型p53（mutp53）的靶向治疗将对癌症治疗产生深远影响。本综述简要讨论了p53突变在癌症中的作用以及通过mRNA纳米医学进展恢复WTp53的治疗潜力。
