Apoptosis, a physiological process of programmed cell death, is disrupted in various malignancies. It has been exploited as an anti-cancer strategy traditionally by inducing DNA damage with chemotherapy and radiotherapy. With an increased understanding of the intrinsic and extrinsic pathways of apoptosis in recent years, novel approaches of targeting the apoptotic pathways have been tested in pre-clinical and clinical models. There are several early phase clinical trials investigating the therapeutic role of pro-apoptotic agents, both as single agents and in combination. In this review, we examine such treatment strategies, detailing the various compounds currently under clinical investigation, their potential roles in cancer therapeutics, and discussing approaches to their optimal use in the clinic.
Keywords: Apoptosis; BH3; Bcl-2; Cancer therapeutics; Extrinsic pathway; IAPs; Intrinsic pathway.
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