Document Detail


Tumor dormancy, oncogene addiction, cellular senescence, and self-renewal programs.
MedLine Citation:
PMID:  23143977     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cancers are frequently addicted to initiating oncogenes that elicit aberrant cellular proliferation, self-renewal, and apoptosis. Restoration of oncogenes to normal physiologic regulation can elicit dramatic reversal of the neoplastic phenotype, including reduced proliferation and increased apoptosis of tumor cells (Science 297(5578):63-64, 2002). In some cases, oncogene inactivation is associated with compete elimination of a tumor. However, in other cases, oncogene inactivation induces a conversion of tumor cells to a dormant state that is associated with cellular differentiation and/or loss of the ability to self-replicate. Importantly, this dormant state is reversible, with tumor cells regaining the ability to self-renew upon oncogene reactivation. Thus, understanding the mechanism of oncogene inactivation-induced dormancy may be crucial for predicting therapeutic outcome of targeted therapy. One important mechanistic insight into tumor dormancy is that oncogene addiction might involve regulation of a decision between self-renewal and cellular senescence. Recent evidence suggests that this decision is regulated by multiple mechanisms that include tumor cell-intrinsic, cell-autonomous mechanisms and host-dependent, tumor cell-non-autonomous programs (Mol Cell 4(2):199-207, 1999; Science 297(5578):102-104, 2002; Nature 431(7012):1112-1117, 2004; Proc Natl Acad Sci U S A 104(32):13028-13033, 2007). In particular, the tumor microenvironment, which is known to be critical during tumor initiation (Cancer Cell 7(5):411-423, 2005; J Clin Invest 121(6):2436-2446, 2011), prevention (Nature 410(6832):1107-1111, 2001), and progression (Cytokine Growth Factor Rev 21(1):3-10, 2010), also appears to dictate when oncogene inactivation elicits the permanent loss of self-renewal through induction of cellular senescence (Nat Rev Clin Oncol 8(3):151-160, 2011; Science 313(5795):1960-1964, 2006; N Engl J Med 351(21):2159-21569, 2004). Thus, oncogene addiction may be best modeled as a consequence of the interplay amongst cell-autonomous and host-dependent programs that define when a therapy will result in tumor dormancy.
Authors:
David I Bellovin; Bikul Das; Dean W Felsher
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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:  2013-04-04     Revised Date:  2013-09-18    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  91-107     Citation Subset:  IM    
Affiliation:
Department of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305-5151, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
CD4-Positive T-Lymphocytes / immunology
Cell Aging*
Cell Cycle Checkpoints
Cell Differentiation
Computational Biology / methods
Early Detection of Cancer / methods
Gene Expression Regulation, Neoplastic*
Humans
Immunologic Factors / immunology,  therapeutic use
Mice
Models, Biological
Molecular Targeted Therapy
Neoplasms / genetics,  immunology,  pathology*,  therapy
Neoplastic Stem Cells / immunology,  metabolism,  pathology
Oncogenes*
Proto-Oncogene Proteins c-myc / genetics,  metabolism
Signal Transduction
Transcriptional Activation*
Tumor Markers, Biological / metabolism
Tumor Microenvironment
Grant Support
ID/Acronym/Agency:
P50 CA114747/CA/NCI NIH HHS; R01 CA170378/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Immunologic Factors; 0/Myc protein, mouse; 0/Proto-Oncogene Proteins c-myc; 0/Tumor Markers, Biological
Comments/Corrections

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