Small molecule compounds targeting the p53 pathway: are we finally making progress?

Yu, X., Narayanan, S., Vazquez, A. and Carpizo, D. R. (2014) Small molecule compounds targeting the p53 pathway: are we finally making progress? Apoptosis, 19(7), pp. 1055-1068. (doi: 10.1007/s10495-014-0990-3) (PMID:24756955) (PMCID:PMC4039992)

Abstract

Loss of function of p53, either through mutations in the gene or through mutations to other members of the pathway that inactivate wild-type p53, remains a critically important aspect of human cancer development. As such, p53 remains the most commonly mutated gene in human cancer. For these reasons, pharmacologic activation of the p53 pathway has been a highly sought after, yet unachieved goal in developmental therapeutics. Recently progress has been made not only in the discovery of small molecules that target wild-type and mutant p53, but also in the initiation and completion of the first in-human clinical trials for several of these drugs. Here, we review the current literature of drugs that target wild-type and mutant p53 with a focus on small-molecule type compounds. We discuss common means of drug discovery and group them according to their common mechanisms of action. Lastly, we review the current status of the various drugs in the development process and identify newer areas of p53 tumor biology that may prove therapeutically useful.

• Item Type: Articles
• Additional Information: This work was supported by grants from the following to DRC: National Cancer Institute (K08CA172676-01), Sidney Kimmel Foundation for Cancer Research, and the Pancreatic Cancer Action-Network.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Vazquez, Alexei
• Authors: Yu, X., Narayanan, S., Vazquez, A., and Carpizo, D. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Apoptosis
• Publisher: Springer
• ISSN: 1360-8185
• ISSN (Online): 1573-675X
• Published Online: 23 April 2014
• Copyright Holders: Copyright © 2014 The Author
• First Published: First published in Apoptosis 19(7):1055-1068
• Publisher Policy: Reproduced under a Creative Commons license