Document Detail


Targeting tumor microenvironment with silibinin: promise and potential for a translational cancer chemopreventive strategy.
MedLine Citation:
PMID:  23617249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tumor microenvironment (TME) refers to the dynamic cellular and extra-cellular components surrounding tumor cells at each stage of the carcinogenesis. TME has now emerged as an integral and inseparable part of the carcinogenesis that plays a critical role in tumor growth, angiogenesis, epithelial to mesenchymal transition (EMT), invasion, migration and metastasis. Besides its vital role in carcinogenesis, TME is also a better drug target because of its relative genetic stability with lesser probability for the development of drug-resistance. Several drugs targeting the TME (endothelial cells, macrophages, cancer-associated fibroblasts, or extra-cellular matrix) have either been approved or are in clinical trials. Recently, non-steroidal anti-inflammatory drugs targeting inflammation were reported to also prevent several cancers. These exciting developments suggest that cancer chemopreventive strategies targeting both tumor and TME would be better and effective towards preventing, retarding or reversing the process of carcinogenesis. Here, we have reviewed the effect of a well established hepatoprotective and chemopreventive agent silibinin on cellular (endothelial, fibroblast and immune cells) and non-cellular components (cytokines, growth factors, proteinases etc.) of the TME. Silibinin targets TME constituents as well as their interaction with cancer cells, thereby inhibiting tumor growth, angiogenesis, inflammation, EMT, and metastasis. Silibinin is already in clinical trials, and based upon completed studies we suggest that its chemopreventive effectiveness should be verified through its effect on biological end points in both tumor and TME. Overall, we believe that the chemopreventive strategies targeting both tumor and TME have practical and translational utility in lowering the cancer burden.
Authors:
Gagan Deep; Rajesh Agarwal
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current cancer drug targets     Volume:  13     ISSN:  1873-5576     ISO Abbreviation:  Curr Cancer Drug Targets     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-07-03     Completed Date:  2014-01-30     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  101094211     Medline TA:  Curr Cancer Drug Targets     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  486-99     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / therapeutic use*
Humans
Neoplasms / drug therapy*
Silymarin / therapeutic use*
Translational Medical Research*
Tumor Microenvironment / drug effects*
Grant Support
ID/Acronym/Agency:
CA102514/CA/NCI NIH HHS; CA112304/CA/NCI NIH HHS; R01 CA102514/CA/NCI NIH HHS; R01 CA112304/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Silymarin; 4RKY41TBTF/silybin
Comments/Corrections

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