Therapeutic potential of combating cancer by restoring wild-type p53 through mRNA nanodelivery

Nanomedicine. 2024 Feb:56:102732. doi: 10.1016/j.nano.2024.102732. Epub 2024 Jan 8.

Abstract

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.

Keywords: Gene therapy; Nanotechnology; Restoring wild-type p53; cancer; p53 mutant.

Publication types

  • Review

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Mutation
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • RNA, Messenger / genetics
  • Transcription Factors / genetics
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53
  • RNA, Messenger
  • Transcription Factors