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Updated: Jul 9, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Restoration of p53 to limit tumor growth
1Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Purpose Of Review:
p53 mutation occurs in over half of all human tumors. Among the remaining tumors, although they may process a wild-type p53, the pathways of p53-induced cell-cycle arrest and apoptosis are deficient. Therefore, p53 serves as a unique molecular target for cancer therapy. This review focuses on the current progress regarding restoration of p53 function in human tumors for molecularly targeted therapy.
Recent Findings:
Targeting p53 for cancer therapy has been intensively pursued. CP-31398 was the first small molecule identified with the ability to restore the wild-type conformation to mutant p53. Subsequently, PRIMA-1 and ellipticine were found to be able to induce mutant p53-dependent cell death. Nutlin was developed to rescue wild-type p53 from degradation mediated by MDM2. More recently, p53 family members can be activated and therefore serve as substitutes of p53 in tumor cells and induce cell death.
Summary:
Loss of p53 function is a characteristic of almost all human tumors. Recent advances demonstrate that reconstitution of p53 function is possible and practical as a promising antitumor strategy.
Insights
Restoring p53 function is a promising cancer therapy strategy. Researchers are developing targeted therapies to reactivate p53 pathways or utilize p53 family members in tumors with deficient p53 function.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- The tumor suppressor protein p53 is frequently inactivated in human cancers through mutation or pathway disruption.
- Restoring p53 function presents a unique molecular target for developing novel cancer therapies.
Purpose of the Study:
- To review current progress in restoring p53 function for molecularly targeted cancer therapy.
- To highlight strategies for addressing p53 deficiency in human tumors.
Main Methods:
- Review of small molecules targeting mutant p53 conformation (e.g., CP-31398).
- Exploration of compounds inducing mutant p53-dependent cell death (e.g., PRIMA-1, ellipticine).
- Investigation of strategies to stabilize wild-type p53 (e.g., Nutlin targeting MDM2).
- Activation of p53 family members as alternative therapeutic approaches.
Main Results:
- CP-31398 identified as the first small molecule to restore wild-type p53 conformation in mutants.
- PRIMA-1 and ellipticine demonstrated efficacy in inducing mutant p53-dependent cell death.
- Nutlin developed to prevent wild-type p53 degradation by MDM2.
- Activation of p53 family members shows potential as a substitute for p53 function.
Conclusions:
- Loss of p53 function is nearly universal in human tumors.
- Reconstituting p53 function is a feasible and promising strategy for cancer treatment.
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