Role of autophagy in tumor progression and regression. In Targeting autophagy in cancer therapy. (Book Chapter)

Depending on tumor type, stage, and genetic context, autophagy can play an opposite role in cancer by promoting tumor progression or regression. It is now well established that autophagy limits tumor initiation, however, it promotes the progression of well-established tumors. In the context of tumor progression and immune response, experimental evidence indicate that autophagy plays a key role in maintaining survival of tumor cells under stress condition such as hypoxia. Indeed, by activating autophagy, tumor cells are able to escape immunosurveillance by activating several overlapping mechanisms in cancer cells. Such findings have inspired significant interest to develop autophagy inhibitor molecules as an entirely new approach to cancer treatment. While much remains to be learned mechanistically, it is now widely established that modulation of this process will be an attractive avenue for future anticancer therapeutic approaches. In this chapter, we will briefly describe the role of autophagy in tumor regression in the context of inflammation, necrosis, oxidative stress and genomic instability. We will also focus on recent reports highlighting the role of autophagy in the impairment of the anti-tumor immune response. In keeping with this, we believe that targeting autophagy may represent a conceptual realm for new anti-tumor strategies aiming to block immune escape.