The role of apoptosis in cancer cell survival and therapeutic outcome.

A number of discoveries have clarified the molecular mechanism of apoptosis, thus clarifying the link between apoptosis and therapeutic outcome. Even though apoptosis is thought to play a major role in anticancer therapy, the clinical relevance of induction of apoptosis remains uncertain, particularly in solid tumors. Induction of apoptosis by anti-cancer agents has been shown to correlate with tumor response, however, non-apoptotic forms of cell death, such as autophagy and extrinsic senescence, have also been shown to contribute to the overall tumor response. Cellular damage induces growth arrest and tumor suppression by inducing apoptosis, necrosis, and senescence; the mechanism of cell death depends on the magnitude of DNA damage following exposure to various concentrations of anticancer agents. Apoptosis-resistant cells and transduction pathways which inhibit apoptosis can induce non-apoptotic mechanisms of cell death and senescence, thereby preserving the antitumor effect of some anticancer agents. Heterogeneic anti-tumor responses include various cell types of cell death, depending on the degree of cellular or DNA damage incurred by cancer cells. As a new therapeutic strategy, alternative types of cell death might be exploited to control and eradicate cancer cells. This review discusses the clinical significance of apoptosis, as well as the potential contribution of other types of cell death to overall tumor sensitivity in the hopes that new therapeutic strategies might follow.