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PMID: 21209413 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

The p53 pathway as a target in cancer therapeutics: obstacles and promise.

Science translational medicine ·Vol. 3 ·No. 64 ·2011-01-05 ·Pages 64rv1

Mandinova A, Lee SW

Abstract

A large fraction of human tumors carry p53 mutations, which allow tumor initiation and progression; furthermore, it is now clear that restoration or reactivation of wild-type p53 function prompts rapid elimination of tumors. The discovery and design of compounds that reactivate or enhance the p53 pathway has resulted in the identification of promising drug candidates that have now entered clinical trials for anticancer strategies. However, some of these agents appear to elicit undesirable toxic effects on normal cells and tissues and therefore are restricted in the dose that can be applied in tumors. In this Review, we discuss the concerns about and promise of these p53 activators and propose ways to expand and optimize screening strategies to identify such molecules.

MeSH Terms
Antineoplastic Agents/therapeutic use Humans Models, Biological Neoplasms/drug therapy,metabolism Signal Transduction/drug effects Tumor Suppressor Protein p53/metabolism
Chemicals
Antineoplastic Agents Tumor Suppressor Protein p53
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mandinova Anna
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Lee Sam W
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Article Info
Journal
Science translational medicine
Abbr.
Sci Transl Med
ISSN
1946-6242
DOI
10.1126/scitranslmed.3001366
Published
2011-01-05
Pages
64rv1
Language
English
Region
United States
NLM ID
101505086
PMCID
PMC3763710
Subset
IM
Grants
NCI NIH HHS · 1R01CA149477 · United States
NCI NIH HHS · R01 CA149477 · United States
NCI NIH HHS · 5P01 CA80058 · United States
NCI NIH HHS · R01 CA142805 · United States
NCI NIH HHS · 5R01CA127247 · United States
NCI NIH HHS · P01 CA080058 · United States
NCI NIH HHS · 2R01CA085681 · United States
NCI NIH HHS · R01 CA140615 · United States
NCI NIH HHS · R01 CA127247 · United States
NCI NIH HHS · 5R01CA140615 · United States
NCI NIH HHS · R01 CA140615-03 · United States
NCI NIH HHS · R01 CA085681 · United States
NCI NIH HHS · 1R01CA142805 · United States
External Links
PubMed source DOI: 10.1126/scitranslmed.3001366 PMC Full Text View journal details
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