Beneficial Outcomes of Cancer Therapeutic Modalities Based on Targeting Apoptosis.

Abstract

In the clinical setting, anticancer therapy is routinely administered to stimulate programmed cell death or "apoptosis." The goal is to eliminate tumor cells. Whether selective activation of apoptosis facilitates aggressive disease relapse in the longer term is still unaddressed. Apoptosis defects have a crucial role in cancer progression and carcinogenesis. Thus, targeting apoptosis may be important in developing new cancer therapeutic modalities. We summarize the shift in thinking that, while apoptosis is a barrier to oncogenesis, it paradoxically drives cancer formation and progression when executed incompletely, i.e., sublethal apoptosis. Also, we review apoptotic mechanisms, the role of apoptosis in carcinogenesis, and how it contributes to cancer treatment. Most current research focuses on the extent of cell death in vitro, but no evidence exists that protein regulation of cell death in vitro is similar to what happens in vivo. Future research requires identifying targets upstream and downstream of such proteins through identifying protein-protein interactions in different survival/apoptosis pathways. Finding nexuses where such pathways interconnect is critical, along with possible mechanisms for regulation.