Hypothesized phases in the induction of apoptosis in response to chemotherapeutic agents. In phase I, cytotoxic agents impart damage to a critical component of the cell such as DNA or microtubules. In phase II, the cell recognizes the damage and its degree of severity through poorly characterized signaling mechanisms. In phase III, the cell assesses the extent of damage and decides on the appropriate response. In many cancer cells, the preferred response is the induction of apoptosis, whereas in most normal cells and in many cancer cells, the response may involve growth arrest to allow for repair. It is also possible that certain cells may react to damage by undergoing senescence or terminal cell differentiation. Cancer cells may acquire resistance to apoptosis at several points in this pathway. For example, mutant p53 may impart resistance to DNA-damaging agents; mutations may exist in the signaling phase (phase II) or in the apoptotic phase III such as with mutant Bcl-2, mutant ras, or hyperactive protein kinase C (PKC).