Targeting the Oncogenic p53 Mutants in Colorectal Cancer and Other Solid Tumors

Int J Mol Sci. 2019 Nov 28;20(23):5999. doi: 10.3390/ijms20235999.

Abstract

Colorectal cancer (CRC) is a kind of solid tumor and the third most common cancer type in the world. It is a heterogeneous disease characterized by genetic and epigenetic aberrations. The TP53 mutation is the key step driving the transition from adenoma to adenocarcinoma. The functional roles of TP53 mutation in tumor development have been comprehensively investigated. In CRC, TP53 mutation was associated with poor prognosis and chemoresistance. A gain of function (GOF) of p53 mutants promotes cell proliferation, migration and invasion through multiple mechanisms. Restoring wild type p53 function, depleting p53 mutants, or intervention by targeting the oncogenic downstreams provides potential therapeutic strategies. In this review, we comprehensively summarize the GOF of p53 mutants in CRC progression as well as in some other solid tumors, and discuss the current strategies targeting p53 mutants in malignancies.

Keywords: TP53; colorectal cancer; p53 mutants; solid tumor.

Publication types

  • Review

MeSH terms

  • Adenoma / drug therapy
  • Adenoma / genetics*
  • Adenoma / metabolism
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Humans
  • Mutation*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • Tumor Suppressor Protein p53