Therapeutic exploitation of the p53 pathway

Trends Mol Med. 2002;8(4 Suppl):S38-42. doi: 10.1016/s1471-4914(02)02309-2.

Abstract

Analysis of the gene encoding p53 could serve to evaluate the effectiveness of a cancer treatment. Mutations in this gene occur in half of all human cancers, and regulation of the protein is defective in a variety of others. Novel strategies that exploit our knowledge of the function and regulation of p53 are being actively investigated. Strategies directed at treating tumours that have p53 mutations include gene therapy, viruses that only replicate in p53 deficient cells, and the search for small molecules that reactivate mutant p53. Potentiating the function of p53 in a non-genotoxic way in tumours that express wildtype protein can be achieved by inhibiting the expression and function of Mdm2 or viral oncoproteins.

Publication types

  • Review

MeSH terms

  • Adenoviridae / genetics
  • Clinical Trials as Topic
  • Gene Expression Regulation, Neoplastic / physiology
  • Genes, p53 / genetics*
  • Genetic Therapy / methods*
  • Humans
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / therapy*
  • Nuclear Proteins*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-mdm2

Substances

  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2