Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Targeting the p53 Pathway of Apoptosis

Author(s): Joana D. Amaral, Joana M. Xavier, Clifford J. Steer and Cecilia M.P. Rodrigues

Volume 16, Issue 22, 2010

Page: [2493 - 2503] Pages: 11

DOI: 10.2174/138161210791959818

Price: $65


The tumor suppressor protein, p53 is regarded as a key player in tumor suppression, as it promotes growth arrest, apoptosis and cellular senescence, while also blocking angiogenesis. The plethora of mechanisms underlying the p53 efficient death response involves transcriptional activation or repression of target genes, as well as the recently identified microRNAs, and transcription-independent functions. Pathological conditions such as cancer, neurodegeneration, ischemia, cholestasis or atherosclerosis are all strongly associated with deregulated levels of apoptosis in which p53 dysfunction has a prominent role. The effect of targeting cell death signaling proteins has been established in preclinical models of human diseases. In this regard, therapeutic strategies aimed at reactivation of p53 in tumors emerge as a promising approach for the treatment of cancer patients, as well as chemical inhibitors of p53 that may prove effective in suppressing disorders associated with widespread p53 activation. This review highlights recent developments of p53-induced apoptosis in human diseases. In addition, we will discuss controversies arising from the double-edge sword of targeting p53 in disease. Finally, ursodeoxycholic acid (UDCA), an endogenous bile acid used to treat cholestatic liver diseases, was recently described as a fine modulator of the complex control of p53 by Mdm-2. We will also review recent therapeutic strategies and clinical applications of targeted agents, and their progress in drug lead discovery, with particular emphasis on the potential use of UDCA.

Keywords: Apoptosis, drug discovery, liver, Mdm-2, p53, UDCA

« Previous

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy