Document Detail


Implications of endoplasmic reticulum stress, the unfolded protein response and apoptosis for molecular cancer therapy. Part II: targeting cell cycle events, caspases, NF-κB and the proteasome.
MedLine Citation:
PMID:  23480539     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Endoplasmic reticulum stress (ERS), the unfolded protein response (UPR) and apoptosis signal transduction pathways are fundamental to normal cellular homeostasis and survival, but are exploited by cancer cells to promote the cancer phenotype.
OBJECTIVE: Collateral activation of ERS and UPR role players impact on cell growth, cell cycle arrest or apoptosis, genomic stability, tumour initiation and progression, tumour aggressiveness and drug resistance. An understanding of these processes affords promising prospects for specific cancer drug targeting of the ERS, UPR and apoptotic pathways.
METHOD: This review (Part II of II) brings forward the latest developments relevant to the molecular connections among cell cycle regulators, caspases, NF-κB, and the proteasome with ERS and UPR signalling cascades, their functions in apoptosis induction, apoptosis resistance and oncogenesis, and how these relationships can be exploited for targeted cancer therapy.
CONCLUSION: Overall, ERS, the UPR and apoptosis signalling cascades (the molecular therapeutic targets) and the development of drugs that attack these targets signify a success story in cancer drug discovery, but a more reductionist approach is necessary to determine the precise molecular switches that turn on antiapoptotic and pro-apoptotic programmes.
Authors:
Donavon C Hiss; Gary A Gabriels
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Publication Detail:
Type:  Journal Article     Date:  2009-06-25
Journal Detail:
Title:  Expert opinion on drug discovery     Volume:  4     ISSN:  1746-0441     ISO Abbreviation:  Expert Opin Drug Discov     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2013-03-13     Completed Date:  2013-03-14     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  101295755     Medline TA:  Expert Opin Drug Discov     Country:  England    
Other Details:
Languages:  eng     Pagination:  907-21     Citation Subset:  -    
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