Document Detail


Sensitization of tumor cells by targeting histone deacetylases.
MedLine Citation:
PMID:  22120677     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Epigenetic mechanisms may contribute to drug resistance by interfering with tumor growth regulatory pathways and pro-apoptotic programs. Since gene expression is regulated by acetylation status of histones, a large variety of histone deacetylase (HDAC) inhibitors have been studied as antitumor agents. On the basis of their pro-apoptotic activity, HDAC inhibitors have been combined with conventional antitumor agents or novel target-specific agents to increase susceptibility to apoptosis and drug sensitivity of cancer cells. Several combination strategies including HDAC inhibitors have been explored in preclinical studies. Promising therapeutic effects have been reported in combination with DNA damaging agents, taxanes, targeted agents, death receptor agonists and hormonal therapies. Some histone deacetylases, such as HDAC6, can also modulate the function of non-histone proteins involved in critical regulatory processes which may be relevant as therapeutic targets. Given the pleiotropic effects of most of the available inhibitors, the mechanisms of the sensitization are not completely elucidated. A better understanding of the involved mechanisms will provide a rational basis to improve the therapeutic outcome of the available antitumor agents.
Authors:
Paola Perego; Valentina Zuco; Laura Gatti; Franco Zunino
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-22
Journal Detail:
Title:  Biochemical pharmacology     Volume:  -     ISSN:  1873-2968     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
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