Autophagy and cancer--issues we need to digest.

Autophagy is an evolutionarily conserved catabolic pathway that has multiple roles in carcinogenesis and cancer therapy. It can inhibit the initiation of tumorigenesis through limiting cytoplasmic damage, genomic instability and inflammation, and the loss of certain autophagy genes can lead to cancer. Conversely, autophagy can also assist cells in dealing with stressful metabolic environments, thereby promoting cancer cell survival. In fact, some cancers rely on autophagy to survive and progress. Furthermore, tumour cells can exploit autophagy to cope with the cytotoxicity of certain anticancer drugs. By contrast, it appears that certain therapeutics require autophagy for the effective killing of cancer cells. Despite these dichotomies, it is clear that autophagy has an important, if complex, role in cancer. This is further exemplified by the fact that autophagy is connected with major cancer networks, including those driven by p53, mammalian target of rapamycin (mTOR), RAS and glutamine metabolism. In this Commentary, we highlight recent advances in our understanding of the role that autophagy has in cancer and discuss current strategies for targeting autophagy for therapeutic gain.