Apoptosis and its clinical impact

Background. Apoptosis or programmed cell death is an orderly cascade that can 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 caspases. These proteases cleave distinct protein substrates, resulting in the morphologic changes seen in apoptosis. This form of cell death is involved in almost every physiologic and pathogenic process in the body. For this reason 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 involved 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 given to examining the relationship between apoptosis and certain disease processes. This review specifically focuses on the importance of apoptosis research in the development of new methods of management of cancer with an emphasis 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 evolving. On the basis of increasing knowledge of how programmed cell death is regulated and the improvements in designing and developing gene therapies and chemicals that are more accurate in targeting specific molecules, the control of apoptosis will become more important in the clinical setting. This possibility will open the door for new therapeutic endeavors in many areas of medicine and specifically in the area of oncology. (C) 2001 John Wiley & Sons, Inc.