Tp53 and its potential therapeutic role as a target in bladder cancer

ABSTRACT

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.

KEYWORDS:

• P53
• TP53
• bladder cancer
• oncotarget
• personalized medicine

Article highlights

• Bladder Cancer is the most common malignancy of the urinary tract and comprises two long-recognized entities with distinct molecular features and clinical outcome.

• The identification of the genetic alterations may lead to the understanding of the nature of this disease and provide the possibility of more efective treatment.

• p53, a tumor suppressor involved in a number of cellular processes, is regulated by the Mdm2, an oncoprotein that acts blocking its ability to regulate target genes.

• Mutations in the p53, frequently observed in human cancer, is an event with prognostic significance in patients with Bladder Cancer.

• MDM2-p53 negative feedback loop has been widely studied and presents an attractive target for cancer therapy. Therapeutic approach by restoring functional p53 protein using small peptides o molecules in cancer cells is now in process.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.