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Inhibition of p53 inhibitors: progress, challenges and perspectives
Gema Sanz, Madhurendra Singh, Sylvain Peuget, and Galina Selivanova*
Department of Microbiology, Tumor and Cell Biology, Biomedicum 8C, Karolinska Institute, SE17165, Sweden
*Correspondence to:Galina Selivanova, E-mail: Galina.Selivanova@ki.se
J Mol Cell Biol, Volume 11, Issue 7, July 2019, Pages 586-599  https://doi.org/10.1093/jmcb/mjz075
Keyword: p53, tumor suppression, anti-cancer therapy, targeted drugs, transcription factor, immune response

p53 is the major tumor suppressor and the most frequently inactivated gene in cancer. p53 could be disabled either by mutations or by upstream negative regulators, including, but not limited to MDM2 and MDMX. p53 activity is required for the prevention as well as for the eradication of cancers. Restoration of p53 activity in mouse models leads to the suppression of established tumors of different origin. These findings provide a strong support to the anti-cancer strategy aimed for p53 reactivation. In this review, we summarize recent progress in the development of small molecules, which restore the tumor suppressor function of wild-type p53 and discuss their clinical advance. We discuss different aspects of p53-mediated response, which contribute to suppression of tumors, including non-canonical p53 activities, such as regulation of immune response. While targeting p53 inhibitors is a very promising approach, there are certain limitations and concerns that the intensive research and clinical evaluation of compounds will hopefully help to overcome.