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The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches

Joerger, Andreas C., Fersht, Alan R.·2016·Annual Review of Biochemistry
DOI 10.1146/annurev-biochem-060815-014710
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Abstract

Inactivation of the transcription factor p53, through either direct mutation or aberrations in one of its many regulatory pathways, is a hallmark of virtually every tumor. In recent years, screening for p53 activators and a better understanding of the molecular mechanisms of oncogenic perturbations of p53 function have opened up a host of novel avenues for therapeutic intervention in cancer: from the structure-guided design of chemical chaperones to restore the function of conformationally unstable p53 cancer mutants, to the development of potent antagonists of the negative regulators MDM2 and MDMX and other modulators of the p53 pathway for the treatment of cancers with wild-type p53. Some of these compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, personalized anticancer medicines. We trace the structural evolution of the p53 pathway, from germ-line surveillance in simple multicellular organisms to its pluripotential role in humans.

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Metadata

Authors
Joerger, A. C., & Fersht, A. R.
Venue
Annual Review of Biochemistry
Publisher
Annual Reviews
Published
2016-06-02
Volume
85
Issue
1
Pages
375-404
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
DOI
10.1146/annurev-biochem-060815-014710
OpenAlex
W2175728132
Cited by
661
References
30
FWCI
6.21
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches. https://app.cochat.ai/papers/10.1146/annurev-biochem-060815-014710
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Joerger, A. C., & Fersht, A. R. (2016). The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches. Annual Review of Biochemistry. https://doi.org/10.1146/annurev-biochem-060815-014710

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