Tumor Dormancy, Oncogene Addiction, Cellular Senescence, and Self-Renewal Programs

  • David I. Bellovin
  • Bikul Das
  • Dean W. FelsherEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 734)


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.


Tumor Microenvironment Minimal Residual Disease Cellular Senescence Immune Effector Tumor Dormancy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to acknowledge current members of the Felsher laboratory for critical discussion and previous members who have contributed to characterizing various models of oncogene addiction.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • David I. Bellovin
    • 1
  • Bikul Das
    • 1
  • Dean W. Felsher
    • 1
    Email author
  1. 1.Division of Oncology, Departments of Medicine and PathologyStanford University School of MedicineStanfordUSA

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