A Senescence Program Controlled by p53 and p16INK4a Contributes to the Outcome of Cancer Therapy

摘要: p53 and INK4a/ARF mutations promote tumorigenesis drug resistance, in part, by disabling apoptosis. We show that primary murine lymphomas also respond to chemotherapy engaging a senescence program controlled p16INK4a. Hence, tumors with or mutations—but not those lacking ARF alone—respond poorly cyclophosphamide therapy vivo. Moreover, harboring Bcl2-mediated apoptotic block undergo drug-induced cytostasis involving the accumulation of p53, p16INK4a, markers, typically acquire INK4a upon progression terminal stage. Finally, mice bearing capable have much better prognosis following than defects. Therefore, cellular contributes treatment outcome