Review
Nature Reviews Drug Discovery 7, 1031-1040 (December 2008) | doi:10.1038/nrd2759
Focus on: Apoptosis
Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-
B pathways
Anwesha Dey1, Vinay Tergaonkar2 & David P. Lane1 About the authors
Abstract
The p53 and nuclear factor-
B (NF-B) pathways play crucial roles in human cancer, in which inactivation of p53 and hyperactivation of NF-B is a common occurrence. Activation of p53 and inhibition of NF-B promotes apoptosis. Although drugs are being designed to selectively activate p53 or inhibit NF-B, there is no concerted effort yet to deliberately make drugs that can simultaneously do both. Recent results suggest that a surprising selection of small molecules have this desirable dual activity. In this Review we describe the principles behind such dual activities, describe the current candidate molecules and suggest mechanisms and approaches to their further development.
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Author affiliations
- Laboratory of Cell Cycle Control, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore.
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Laboratory of NF-B Signalling in Human Ailments, Institute of Molecular and Cell Biology, Proteos.
Correspondence to: Vinay Tergaonkar2 Email: vinayt@imcb.a-star.edu.sg
Correspondence to: David P. Lane1 Email: d.p.lane@imcb.a-star.edu.sg
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