Abstract
The tumour suppressor p53 is at the centre of a network of regulatory pathways that guard over the continued integrity of the living cell and its progeny after exposure to different forms of stress, particularly those capable of inducing DNA damage. Tumour cells very frequently circumvent this control by disabling the function of p53, or other proteins in the p53 network, through mutation. Here we review the different therapeutic strategies that have been adopted to exploit common neoplastic aberrations in the p53 pathways. We emphasise in particular those approaches where modulation with pharmaceutical agents has already shown some promise, including pharmacological rescue of mutant p53, modulation of the protein-protein interaction between p53 and one of its negative regulators, Mdm2, as well as interference with downstream targets.
Keywords: p53-Mdm2 Pathway, protein
Mini-Reviews in Medicinal Chemistry
Title: The p53-Mdm2 Pathway: Targets for the Development of New Anticancer Therapeutics
Volume: 3 Issue: 3
Author(s): Daniella I. Zheleva, David P. Lane and Peter M. Fischer
Affiliation:
Keywords: p53-Mdm2 Pathway, protein
Abstract: The tumour suppressor p53 is at the centre of a network of regulatory pathways that guard over the continued integrity of the living cell and its progeny after exposure to different forms of stress, particularly those capable of inducing DNA damage. Tumour cells very frequently circumvent this control by disabling the function of p53, or other proteins in the p53 network, through mutation. Here we review the different therapeutic strategies that have been adopted to exploit common neoplastic aberrations in the p53 pathways. We emphasise in particular those approaches where modulation with pharmaceutical agents has already shown some promise, including pharmacological rescue of mutant p53, modulation of the protein-protein interaction between p53 and one of its negative regulators, Mdm2, as well as interference with downstream targets.
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Cite this article as:
Zheleva I. Daniella, Lane P. David and Fischer M. Peter, The p53-Mdm2 Pathway: Targets for the Development of New Anticancer Therapeutics, Mini-Reviews in Medicinal Chemistry 2003; 3 (3) . https://dx.doi.org/10.2174/1389557033488178
DOI https://dx.doi.org/10.2174/1389557033488178 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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