Autophagy and cancer metabolism-The two-way interplay.

Autophagy is an intracellular catabolic process that degrades cytoplasmic components for recycling in response to stressed conditions, such as nutrient deprivation. Dysregulation of autophagy is associated with various diseases, including cancer. Although autophagy plays dichotomous and context-dependent roles in cancer, evidence has emerged that cancer cells exploit autophagy for metabolic adaptation. Autophagy is upregulated in many cancer types through tumor cell-intrinsic proliferation demands and the hypoxic and nutrient-limited tumor microenvironment (TME). Autophagy-induced breakdown products then fuel into various metabolic pathways to supply tumor cells with energy and building blocks for biosynthesis and survival. This bidirectional regulation between autophagy and tumor constitutes a vicious cycle to potentiate tumor growth and therapy resistance. In addition, the pro-tumor functions of autophagy are expanded to host, including cells in TME and distant organs. Thus, inhibition of autophagy or autophagy-mediated metabolic reprogramming may be a promising strategy for anticancer therapy. Better understanding the metabolic rewiring mechanisms of autophagy for its pro-tumor effects will provide insights into patient treatment.