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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Targeting p53 in cancer
1Novartis, Oncology Department, Basel CH-4002, Switzerland. patrick_chene@yahoo.com
Abstract:
The loss of p53 function is a very important event in cancer. The absence of a functional p53 in tumours favours cancer development, and it has been suggested that it also influences the efficacy of both chemotherapy and radiotherapy. The p53 pathway is therefore the subject of intense research, both in academia and in industry, to identify new compounds targeting tumours with an altered p53. Different strategies are currently under investigation. They can be divided into two groups: biological and chemical strategies. The biological strategies utilise the immune system to eliminate the tumours overexpressing p53 mutants. Alternatively they use vectors delivering a functional p53 gene in tumours or engineered viruses, which selectively target p53-defective cells. The chemical strategies are based on the design of compounds that stabilise or activate the p53 mutant proteins, inhibit the interaction between p53 and hdm2, or act on the p53-binding chaperone proteins. In this review, the current progress in these different approaches will be analysed.
Insights
Loss of p53 function accelerates cancer development and impacts treatment efficacy. Research focuses on targeting altered p53 pathways using biological and chemical strategies to improve cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Loss of p53 function is a critical event in cancer development.
- Altered p53 influences the effectiveness of chemotherapy and radiotherapy.
- The p53 pathway is a key target for anti-cancer drug development.
Purpose of the Study:
- To review current progress in strategies targeting tumors with altered p53.
- To analyze biological and chemical approaches for p53-targeted cancer therapy.
Main Methods:
- Review of current academic and industrial research on p53.
- Categorization of strategies into biological and chemical approaches.
- Analysis of specific therapeutic tactics within each strategy.
Main Results:
- Biological strategies involve immunotherapy, gene therapy, and oncolytic viruses.
- Chemical strategies focus on stabilizing/activating p53 mutants, inhibiting p53-hdm2 interactions, or targeting chaperones.
- Diverse approaches are under investigation to exploit p53 alterations in cancer.
Conclusions:
- Targeting the p53 pathway offers promising avenues for novel cancer treatments.
- Both biological and chemical strategies present distinct but potentially synergistic therapeutic opportunities.
- Continued research is essential to translate these strategies into effective clinical applications.
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