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Targeting Therapies for the p53 Protein in Cancer Treatments

Authors
  • Levine, Arnold J.
Type
Published Article
Journal
Annual Review of Cancer Biology
Publisher
Annual Reviews
Publication Date
Mar 04, 2019
Volume
3
Pages
21–34
Identifiers
DOI: 10.1146/annurev-cancerbio-030518-055455
Source
Annual Reviews
Keywords
License
Yellow

Abstract

Half of all human cancers contain TP53 mutations, and in many other cancers, the function of the p53 protein is compromised. The diversity of these mutations and phenotypes presents a challenge to the development of drugs that target p53 mutant cancer cells. This review describes the rationale for many different approaches in the development of p53 targeted therapies: (a) viruses and gene therapies, (b) increased levels and activity of wild-type p53 proteins in cancer cells, (c) p53 protein gain-of-function inhibitors, (d) p53 protein loss-of-function structural correctors, (e) mutant p53 protein synthetic lethal drugs interfering with the p53 pathway, and (f) cellular immune responses to mutant p53 protein antigens. As these types of therapies are developed, tested, and evaluated, the best of them will have a significant impact upon cancer treatments and possibly prevention.

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