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Small Molecules Targeting Mutant P53: A Promising Approach for Cancer Treatment

Elizabeth A Lopes1, Sara Gomes2, Lucília Saraiva2

  • 1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.

Current Medicinal Chemistry
|November 17, 2018
PubMed

Insights

Mutant p53 proteins are common in many cancers and linked to poor outcomes. Reactivating mutant p53 with drugs is a promising strategy, but new, safer options are needed.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Over 50% of human tumors harbor mutations in the p53 tumor suppressor gene.
  • Mutant p53 expression correlates with increased tumor invasiveness, chemoresistance, and poor patient prognosis.
  • Restoring wild-type p53 activity presents a potential therapeutic avenue for various cancers.

Purpose of the Study:

  • To review key small molecule compounds designed to reactivate mutant p53.
  • To assess the current landscape of mutant p53 reactivators in preclinical and clinical development.
  • To highlight the need for novel pharmacological agents with improved selectivity and safety profiles.

Main Methods:

  • Literature review of scientific publications and clinical trial data.
  • Analysis of small molecule mutant p53 reactivators.
  • Evaluation of drug efficacy, selectivity, and toxicity.

Main Results:

  • Several small molecule compounds targeting mutant p53 have been identified and developed.
  • Some compounds have advanced to clinical trials for various cancer types.
  • No mutant p53 reactivator has yet reached clinical approval, indicating ongoing challenges.

Conclusions:

  • Targeting mutant p53 reactivation is a viable anticancer strategy.
  • Further research is essential to develop more effective and safer mutant p53 reactivators.
  • The development of novel pharmacological agents with enhanced selectivity and reduced side effects is critical for clinical success.
Keywords:
Cancerchemotherapymutant p53p53 tumor suppressorreactivatorssmall molecules.

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