Therapeutic targeting of death pathways in cancer: mechanisms for activating cell death in cancer cells.

Defects in apoptosis that evolve during the course of cancer progression not only provide cancer cells with intrinsic survival advantage, but also provide inherent resistance to chemotherapeutic agents. Thus, modulation of apoptosis by targeting components of the apoptotic machinery and its regulators to restore apoptotic function is a rational approach for treating cancer. With our increasing knowledge of the mechanisms of apoptosis regulation and of how apoptosis is disabled in cancer cells, numerous novel approaches targeting apoptotic pathways can now be exploited for cancer therapy. While most of these therapies are still in preclinical development, some have shown considerable promise and progressed into the clinic. This chapter summarizes the current knowledge of the apoptotic pathways and provides a selective review on the development of drugs that target the apoptotic machinery.