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

摘要: Cancers are frequently addicted to initiating oncogenes that elicit aberrant cellular proliferation, self-renewal, and apoptosis. Restoration of normal physiologic regulation can dramatic reversal the neoplastic phenotype, including reduced proliferation increased apoptosis tumor cells (Science 297(5578):63-64, 2002). In some cases, oncogene inactivation is associated with compete elimination a tumor. However, in other induces conversion dormant state differentiation and/or loss ability self-replicate. Importantly, this reversible, regaining self-renew upon reactivation. Thus, understanding mechanism inactivation-induced dormancy may be crucial for predicting therapeutic outcome targeted therapy. One important mechanistic insight into addiction might involve decision between self-renewal senescence. Recent evidence suggests regulated by multiple mechanisms include cell-intrinsic, cell-autonomous host-dependent, 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). particular, microenvironment, which known critical during initiation (Cancer 7(5):411-423, 2005; J Clin Invest 121(6):2436-2446, 2011), prevention (Nature 410(6832):1107-1111, 2001), progression (Cytokine Growth Factor Rev 21(1):3-10, 2010), also appears dictate when elicits permanent through induction senescence (Nat Oncol 8(3):151-160, 2011; 313(5795):1960-1964, 2006; N Engl Med 351(21):2159-21569, 2004). best modeled as consequence interplay amongst host-dependent define therapy will result dormancy.