Tp53 and its potential therapeutic role as a target in bladder cancer
Chiara Ciccarese1, Francesco Massari2, Ana Blanca3
1a Medical Oncology, Azienda Ospedaliera Universitaria Integrata , University of Verona , Verona , Italy.
Introduction:
Despite more than 30 years of research on p53 resulting in >50,000 publications, we are now beginning to figure out the complexity of the p53 pathway, gene ontology and conformational structure of the molecule. Recent years brought great advances in p53 related drugs and the potencial ways in which p53 is inactivated in cancer. Areas covered: We searched for related publications on Pubmed and ClinicalTrial.gov using the following keywords 'p53, Tp53, p53 and bladder cancer, p53 and therapeutic target'. Relevant articles improved the understanding on p53 pathways and their potential as candidate to targeted therapy in bladder cancer. Expert opinion: Novel strategies developed to restore the function of mutants with chemical chaperones or by using compounds to improved pharmacokinetic properties are in development with potential to be applied in the oncology clinic. Other strategies targeting aberrantly overexpressed p53 regulators with wild-type p53 are also an active area of research. In particular, studies inhibiting the interaction of p53 with its negative regulators MDMX and MDM2 are an important field in drug discovery. Small molecules for inhibition of MDM2 are now in clinical trials process. However, personalized anticancer therapy might eventually advance through analyses of p53 status in cancer patients.
Insights
Research on the p53 pathway reveals its complexity and potential as a therapeutic target in bladder cancer. New strategies aim to restore p53 function or inhibit its regulators, advancing personalized oncology.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- The tumor suppressor p53 pathway is complex, with recent advances clarifying its role in cancer.
- Understanding p53 inactivation mechanisms in cancer is crucial for developing targeted therapies.
- Over 50,000 publications exist on p53, yet its full complexity is still being elucidated.
Purpose of the Study:
- To review current understanding of the p53 pathway in bladder cancer.
- To explore novel therapeutic strategies targeting p53 or its regulators.
- To assess the potential of p53 as a therapeutic target in bladder cancer.
Main Methods:
- Literature search on PubMed and ClinicalTrials.gov.
- Keywords used: 'p53, Tp53, p53 and bladder cancer, p53 and therapeutic target'.
- Analysis of relevant articles to synthesize current knowledge and expert opinion.
Main Results:
- Novel strategies are being developed to restore mutant p53 function using chemical chaperones or improved compounds.
- Inhibiting negative regulators like MDM2 and MDMX is a key area in p53 drug discovery.
- Small molecules targeting MDM2 are currently in clinical trials for cancer therapy.
Conclusions:
- Restoring p53 function or targeting its regulators offers promising therapeutic avenues for bladder cancer.
- Personalized anticancer therapy may advance through p53 status analysis in patients.
- Targeted therapies focusing on the p53 pathway hold potential for clinical application in oncology.
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