Autophagy modulation in cancer therapy

Autophagy is a process by which cytoplasmic components are sequestered in double membrane vesicles and degraded upon fusion with lysosomal compartments. Autophagy is utilized by tumor cells to survive metabolic stress and as such autophagy inhibitors are predicted to have clinical value in the setting of cancer therapy. Paradoxically, allelic loss of the essential autophagy gene beclin1 is found with high frequency in human breast, ovarian and prostate cancers, suggesting that impaired autophagy promotes cancer. Probable causes of cancer associated with defects in autophagy and impaired tolerance to stress include enhanced cell death resulting in an inflammatory response and cytokine production, and also genome damage. This suggests that autophagy inducers would also be valuable in the setting of cancer prevention to limit cellular genome damage, cell death and inflammation. As autophagy is a major component of the cellular stress response, modulating the autophagy pathway is a promising new area in cancer prevention and therapy.