Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment


Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms tocontrol cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells froman organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases likecancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible forapoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity ofcancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include thosetargeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP),inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents havebeen assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory moleculesthat control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptoticpathways contribute to cancer, and list several agents being developed to target apoptosis.