Autophagy as a critical driver of metabolic adaptation, therapeutic resistance, and immune evasion of cancer

Autophagy is a well-conserved intracellular degradation pathway. Besides its physiological role in normal cells, autophagy is activated in various cancer types and protects cancer cells from stresses such as nutrient deprivation, therapeutic insults, and antitumor immunity. Autophagy in cancer cells as well as normal cells in the host supports tumor metabolism, allowing for tumor growth under a nutrient-limited tumor microenvironment. Autophagy also protects cancer cells from treatments such as radiation therapy, cytotoxic chemotherapy, and targeted therapy. Though the roles of autophagy in antitumor immunity are complex and highly context-dependent, accumulating evidence now supports the role of autophagy in mediating immunotherapy resistance. Based on these preclinical findings, multiple clinical trials are currently ongoing to test the therapeutic efficacy of autophagy inhibition in cancer. Here, we review recent findings on the tumor-promoting roles of autophagy in cancer and discuss advances in therapeutic approaches that target autophagy in cancer.