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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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A balancing act: using small molecules for therapeutic intervention of the p53 pathway in cancer

Jessica J Miller1, Christian Gaiddon2, Tim Storr1

  • 1Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada. tim_storr@sfu.ca.

Chemical Society Reviews
|September 2, 2020
PubMed

Insights

Small molecules targeting the guardian of the genome, p53, aim to restore its function in cancer. Despite challenges, advancements in personalized medicine offer promise for p53 reactivating compounds in anticancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • The p53 protein, known as the "guardian of the genome", is frequently mutated in cancer, leading to pathway malfunction in nearly all cancer types.
  • Mutant p53 is an overexpressed and tumor-specific target, driving extensive research into small molecule drugs to restore its wild-type function.

Purpose of the Study:

  • This review consolidates and explains the chemical principles behind designing small molecule drugs for misfolded proteins in anticancer therapy.
  • To highlight the challenges and future promise of p53-targeting compounds in cancer treatment.

Main Methods:

  • Review of chemical principles in small molecule drug design.
  • Analysis of challenges and technological advancements in p53 pathway reactivation.

Main Results:

  • Small molecule drug design for mutant p53 faces challenges, including off-target effects causing cytotoxicity independent of p53 status.
  • Significant technological advancements, such as gene sequencing, are improving the development of targeted therapies.

Conclusions:

  • Despite challenges, the development of small molecules to reactivate p53 holds significant promise for cancer therapy.
  • Personalized medicine approaches and technological progress enhance the potential of p53 reactivating compounds for widespread benefit in oncology.

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