Schematic depiction of the autophagy pathway. Autophagy is a multi-step process characterized by the induction, nucleation, extension, and completion of an isolation membrane (phagophore). The initiation of autophagy is regulated by the ULK complex. Nucleation of the phagophore is regulated by the Class III PI3K complex, which consists of Vps34, Beclin1, p150, and ATG14. Membrane elongation requires two ubiquitin-like systems that mediate the formation of ATG12-ATG5 and PE-conjugated ATG8. The completed autophagosome, along with sequestered cargo, ultimately fuses with the lysosome. The resulting autolysosome is a single membrane-bound acidic vesicle where the contents are digested by lysosomal hydrolases and recycled. Further details are provided in the text

Schematic depiction of the tumor suppressive and pro-tumorigenic roles of autophagy during cancer progression and therapy. Tumor suppressive functions of autophagy include: (1) eliminating damaged organelles and mitigating oxidative stress, which prevents genome instability, and ultimately, malignant transformation; (2) promoting oncogene-induced senescence, a barrier to malignant transformation; and (3) preventing necrosis in apoptosis deficient cells in response to metabolic stress, which reduces pro-tumorigenic inflammation. Pro-tumorigenic roles for autophagy include: (1) promoting tumor cell survival in response to diverse micro-enviromental and chemotherapy-induced stresses, and (2) protecting cells from anoikis, which may facilitate drug-resistance and metastasis. Further details are provided in the text