Survival factors suppress apoptosis (A)increased production of (B) inactivation of pro- (C)inactivation of anti-lAPs anti-apoptotic Bcl2 protein apoptotic BH3-only Bcl2 proteIn survival factor survival factor survival factor activated activated activated receptor receptor receptor activated gene regulatory active proteIn Akt kinase MAP-kinase Inactive active Bcl2 Bcl2 NUCLEUS active hid inactive Hid RNA active Bad inactive ⊥ Bcl2 protein APOPTOSIS BLOCKED APOPTOSIS BLOCKED APOPTOSIS BLOCKED
Survival factors suppress apoptosis
P53 a transcription factor,“ Gene guards” HYPERPROLIFERATIVE DNA TELOMERE SIGNALS DAMAGE SHORTENING HYPOXIA stable, active p53 CELL CYCLE ARREST SENESCENCE APOPTOSIS
P53 a transcription factor, “Gene guards
瘟基因和抑癌基因存在相互调节作用 Myc癌基因 异常增殖信号不 77/Ii 定都会引起细 胞恶性增殖 excessive Myc production inactive Mdm2 抑癌基因 Arf 癌基因 active Mdm2 stable, i\ active p53 P53抑癌基因 p53 DEGRADATION cell-cycle OR apoptosis arrest
癌基因和抑癌基因存在相互调节作用 癌基因 抑癌基因 癌基因 抑癌基因 异常增殖信号不 一定都会引起细 胞恶性增殖
C. Cell activities in disease Sustaining proliferative signaling Resisting Evading growth cell death suppressors Inducing Activating invasion angiogenes and metastasis mmortality The hallmarks of cancer 2000.Cell.57-70
The Hallmarks of Cancer 2000, Cell, 57-70 C. Cell activities in disease
Therapeutic Targeting of the hallmarks of Cancer EGFR inhibitors kinase inhibito Sustaining Aerobic glycolysis proliferative growth mmune activating anti-CTLA4 mAb Avoid Proapoptotic Resisting Enabling Telomerase BH3 mimetics ←0 o replicate Inhibitors Tumor PARP duc Activating Selective anti inhibitors angiogenesis invasion inflammatory drugs metastasis Inhibitors of VEGF signalin Cell 144, March 4, 2011
Cell 144, March 4, 2011 Therapeutic Targeting of the Hallmarks of Cancer