A main strategy for treating cancer is to induce cell death.  It is often stated as fact that chemotherapies induce death through apoptotic mechanisms.  The significance of p53 and the Bcl-2 family and other molecules that drive apoptosis has provided the mort opportunities for pharmaceutical exploitation.  With the development of the approaches specifically targeting the impaired apoptosis in cancer cells, however, a paradox in medical oncology has long exist that although the majority of human cancers have acquired a deficiency in apoptosis through p53 mutations or Bcl-2 dysregulation, certain chemotherapeutic agents such as DNA alkylating agents remain the most effective means in curing cancer patients by inducing cancer cell death.  This suggests that alternative cell death pathways independent of apoptosis may be involved in cell death induced by chemotherapeutic treatment.  These include necrosis, autophagy, and cell senescence.  Using cell culture systems and animal tumor models, we study how cell death pathways are regulated, and how they interplay in response to the treatment of anti-cancer drugs.