Chapter title |
Tumor dormancy, oncogene addiction, cellular senescence, and self-renewal programs.
|
---|---|
Chapter number | 6 |
Book title |
Systems Biology of Tumor Dormancy
|
Published in |
Advances in experimental medicine and biology, November 2012
|
DOI | 10.1007/978-1-4614-1445-2_6 |
Pubmed ID | |
Book ISBNs |
978-1-4614-1444-5, 978-1-4614-1445-2
|
Authors |
Bellovin DI, Das B, Felsher DW, David I. Bellovin, Bikul Das, Dean W. Felsher, Bellovin, David I., Das, Bikul, Felsher, Dean W. |
Abstract |
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. |
X Demographics
Geographical breakdown
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Germany | 1 | 50% |
United Kingdom | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 2% |
Russia | 1 | 2% |
Unknown | 60 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 19 | 31% |
Student > Ph. D. Student | 10 | 16% |
Student > Bachelor | 6 | 10% |
Student > Master | 5 | 8% |
Other | 3 | 5% |
Other | 5 | 8% |
Unknown | 14 | 23% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 14 | 23% |
Agricultural and Biological Sciences | 10 | 16% |
Medicine and Dentistry | 8 | 13% |
Immunology and Microbiology | 3 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
Other | 8 | 13% |
Unknown | 17 | 27% |