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

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 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.

Expert opinion on therapeutic targets. 2017 Mar 01 [Epub]

Chiara Ciccarese, Francesco Massari, Ana Blanca, Giampaolo Tortora, Rodolfo Montironi, Liang Cheng, Marina Scarpelli, Maria R Raspollini, Nuno Vau, Jorge Fonseca, Antonio Lopez-Beltran

a Medical Oncology, Azienda Ospedaliera Universitaria Integrata , University of Verona , Verona , Italy., b Medical Oncology , Azienda Ospedaliera Universitaria Integrata (A.O.U.I.) , Verona , Italy., c Maimonides Biomedical Research Institute of Cordoba, Spain - Urology Department , Reina Sofía Hospital , Córdoba , Spain., d Medical Oncology dU, Policlinico 'G.B. Rossi' , University of Verona , Verona , Italy., e Pathological Anatomy , Polytechnic University of the Marche Region, School of Medicine, United Hospitals , Ancona , Italy., f Department of Pathology and Laboratory Medicine , Indiana University School of Medicine , Indianapolis , IN 46202 , USA., g Histopathology and Molecular Diagnostics Service , Careggi University Hospital Florence , Florence , Italy., h Medical Oncology , Champalimaud Clinical Center , Lisbon , Portugal., i Urology service , Champalimaud Clinical Center , Lisbon , Portugal., j Department of Surgery and Pathology , Cordoba University Medical School, Cordoba, Spain and Champalimaud Clinical Center , Lisbon , Portugal.