Apoptosis and its clinical impact

Background. Apoptosis or programmed cell death is an orderly cascade that c an be regulated and ultimately results in the demise of the cell. Induction of apoptosis can occur by various chemical and biologic agents. Initiation of apoptosis leads to activation of effector molecules particularly caspas es. These proteases cleave distinct protein substrates, resulting in the mo rphologic changes seen in apoptosis. This form of cell death is involved in almost every physiologic and pathogenic process in the body. For this reas on the ability to control apoptosis has important therapeutic ramifications . Results. This article reviews the history of the investigation of apoptosis and summarizes the most important pathways and regulatory molecules involv ed in this process. The major regulators of apoptosis, including the Bcl-2, caspase, and inhibitor of apoptosis families, are examined. The two major apoptotic pathways, including the extrinsic/cell surface death receptor and the intrinsic/mitochondrial pathways, are discussed. A major emphasis is g iven to examining the relationship between apoptosis and certain disease pr ocesses. This review specifically focuses on the importance of apoptosis re search in the development of new methods of management of cancer with an em phasis in head and neck oncology. Conclusions. Apoptosis is a rapidly growing field. The understanding of the mechanisms and effector molecules controlling this form of cell death is e volving. On the basis of increasing knowledge of how programmed cell death is regulated and the improvements in designing and developing gene therapie s and chemicals that are more accurate in targeting specific molecules, the control of apoptosis will become more important in the clinical setting. T his possibility will open the door for new therapeutic endeavors in many ar eas of medicine and specifically in the area of oncology. (C) 2001 John Wil ey & Sons, Inc.