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

Expert Opin Ther Targets. 2017 Apr;21(4):401-414. doi: 10.1080/14728222.2017.1297798. Epub 2017 Mar 1.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle Proteins
  • Drug Design
  • Humans
  • Molecular Chaperones / pharmacology
  • Molecular Targeted Therapy
  • Nuclear Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • MDM4 protein, human
  • Molecular Chaperones
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2