Regulation of Apoptosis by Autophagy to Enhance Cancer Therapy

In cancer therapy, a principle goal is to kill cancer cells while minimizing death of normal cells. Traditional cytotoxic therapies and the newer agents that target specific signaling proteins that are critical for cancer cell growth do this by activating a specific type of programmed cell death – apoptosis. However, it has been well established that cancer cells have varying levels of responses to apoptotic stimuli, with some being close to an “apoptotic threshold” and others being further away and that this ultimately determines whether cancer therapy is successful or not. In this review, we will highlight how the underlying mechanisms that control apoptosis thresholds relate to another important homeostatic process in cell survival and cell death, autophagy, and discuss recent evidence suggesting how inhibition of autophagy can enhance the action of anti-cancer drugs by modulating the apoptotic response.