Fig. 1. Modulation of apoptosis sensitivity during oncogenesis. Most normal cells are relatively resistant to stress caused by DNA- or cytoskeleton-damaging agents. Following moderate levels of damage, these cells usually initiate cell-cycle arrest, which is succeeded by damage repair. During the process of oncogenic transformation, both proliferative and stress signals are enhanced, leading to sensitization to apoptotic stimuli. This is the basis for the selectivity of anticancer agents towards neoplastic cells. As tumor cells evolve, they undergo stress-driven selection, which finally endows them with anti-apoptotic armor. Thus, advanced tumor cells usually display a high degree of resistance to stress signals.