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Tumor dormancy: long-term survival in a hostile environment.
MedLine Citation:
PMID:  23143980     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Tumor dormancy occurs when cancer cells are present but the tumor does not grow. Following treatment, patients may enter complete remission in which persistent cells represent the minimal residual disease (MRD). Experimental models and clinical data suggest that the absolute quantity of this MRD is extremely low. Very few cancer cells can persist for years or decades under these hostile conditions that include continuous exposure to maintenance treatment, autologous anti-tumor immune response, and a nonpermissive microenvironment. Dormant tumor cells may survive despite these destruction factors if they adapt and develop strategies to escape from cell death. Escape may result in a state of equilibrium between MRD and the patient. Equilibrium between the immune response and tumor cells can result in long-term tumor dormancy; however, after variable lengths of time, tumor dormancy ends, and the disease progresses. Experimental models have shown that dormant tumor cells may over-express B7-H1 and B7.1 and inhibit cytotoxic T-cellmediated lysis. This resistance could be therapeutically targeted using drugs like MEK inhibitors that modulate pathways involved in B7-H1 expression. Dormant tumor cells may also develop nonspecific resistance mechanisms to cell death, such as deregulation of JAK/STAT and mTORC2/AKT pathways or autocrine and paracrine production of cytokines. This deregulation leads to cross-resistance between the immune response and cytotoxic drugs, indicating that the long-term selection that occurs in vivo during tumor dormancy may ultimately result in resistant relapse. Long-term selection of cancer cells in vitro using tyrosine kinase inhibitors selects cells that harbor the same resistance mechanisms as dormant tumor cells. Elucidating the mechanisms underlying the equilibrium that allows for the persistence of dormant tumor cells presents a novel strategy for targeted drug treatment in the context of maintenance therapy.
Authors:
Bruno Quesnel
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Advances in experimental medicine and biology     Volume:  734     ISSN:  0065-2598     ISO Abbreviation:  Adv. Exp. Med. Biol.     Publication Date:  2013  
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  181-200     Citation Subset:  IM    
Affiliation:
Service des Maladies du Sang, Centre Hospitalier et Universitaire de Lille, Rue Polonovski, 59037, Lille, France, brunoquesnel@hotmail.com.
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