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Updated: Mar 21, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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

Andreas C Joerger1,2,3, Alan R Fersht1

  • 1Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.

Annual Review of Biochemistry
|May 6, 2016
PubMed

Insights

The p53 tumor suppressor is inactivated in most cancers. Novel therapies targeting p53 activators and its regulators, like MDM2 and MDMX, are advancing to clinical trials for personalized cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Inactivation of the transcription factor p53 is a common event in cancer, occurring through direct mutation or dysregulation of its pathways.
  • The p53 pathway plays a crucial role in tumor suppression, acting as a critical cellular safeguard against oncogenic transformation.

Purpose of the Study:

  • To review the therapeutic strategies targeting the p53 pathway for cancer treatment.
  • To explore the evolutionary trajectory of the p53 pathway from simple organisms to humans.

Main Methods:

  • Review of recent advancements in p53 research and therapeutic development.
  • Analysis of structural evolution and functional roles of the p53 pathway across species.

Main Results:

  • Development of novel therapeutic approaches including chemical chaperones for mutant p53 and antagonists for negative regulators (MDM2, MDMX).
  • Several p53-targeting compounds have progressed into clinical trials, indicating promising personalized medicine strategies.
  • The p53 pathway's role has evolved from basic surveillance to a complex, pluripotential function in humans.

Conclusions:

  • Targeting the p53 pathway offers a promising avenue for developing novel, personalized anticancer therapies.
  • Understanding the molecular mechanisms and evolutionary history of p53 is key to unlocking its full therapeutic potential.
Keywords:
cancer therapydrug designp53 familyprotein evolutionsignaling pathwayssmall-molecule stabilizers

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