Apoptosis and its relevance in cancer therapy

In the majority of human tumors the ability to induce programmed cell death (apoptosis) is frequently lost, suggesting that disruption of the apoptoti c function contributes significantly to the transformation of a normal cell into a tumor cell. Apoptosis is regulated by two major pathways, the death receptor-induced and the stress-mediated pathway. While the former depends on the activation of death receptors such as Fas-R, the latter is induced by various stress signals. Stimulation of the death receptor pathway direct ly triggers the proteolytic activation of caspases via the formation of a d eath receptor-induced signalling complex (DISC). In contrast, caspase activ ation via the stress-induced pathway is mediated by the formation of a prot ein complex called apoptosome which forms upon release of cytochrome c regu lated by members of the Bcl-2 protein family. Ultimately, both pathways dis embogue into cellular changes, eventually causing the cell death. Mutation of many different genes involved in the regulation of apoptosis have been i dentified in human cancer, resulting in the development of novel therapeuti c approaches such as activation of death receptors using recombinant ligand or inhibition of Bcl-2 expression by antisense reagents. Although based on different targets and delivery methods, all these approaches have the comm on goal to eliminate tumor cells by restoration of the apoptotic function.