Autophagy, metabolism and cancer

Abstract

Macroautophagy (autophagy) degrades proteins, other macromolecules, and organelles, in lysosomes and recycles the breakdown products to promote survival in stress and starvation. Autophagy is upregulated in some cancers and promotes survival and malignancy, suggesting that targeting autophagy in cancer may be therapeutically advantageous. Autophagy promotes tumor cell autonomous cancer in preclinical models by suppressing p53, apoptosis, senescence, and immune responses, and also by promoting metabolism and proliferation. In host tissues, autophagy promotes cancer by tumor cell non-autonomous mechanisms by providing nutritional support to tumors. Furthermore, the genes encoding the master regulators of autophagy and lysosomal biogenesis are known oncogenes activated in cancer. In other preclinical models, autophagy is inconsequential or promotes chronic liver damage and development of benign hepatomas.  These findings suggest that there is a context-dependent role for autophagy in cancer. Thus, identifying how to target the autophagy pathway, the tumor types that would best respond to autophagy inhibition, the mechanism involved, and what drug combinations would work best, is of great interest.