Autophagy as a cytoprotective mechanism in esophageal squamous cell carcinoma

•Clinical studies support autophagy effectors as prognostic biomarkers in ESCC.•Autophagy promotes invasion and cancer stem cell expansion/maintenance in ESCC.•Autophagy inhibition improves therapeutic efficacy in preclinical ESCC models.•The mechanistic contribution of autophagy to ESCC biology and therapy response remain elusive. Esophageal squamous cell carcinoma (ESCC) is amongst the most aggressive human malignancies, representing a significant health burden worldwide. Autophagy is an evolutionarily conserved catabolic process that degrades and recycles damaged organelles and misfolded proteins to maintain cellular homeostasis. Alterations in autophagy are associated with cancer pathogenesis, including ESCC; however, the functional role of autophagy in ESCC remains elusive. Here, we discuss the clinical relevance of autophagy effectors in ESCC and review current knowledge regarding the molecular mechanisms through which autophagy contributes to ESCC. We highlight the cytoprotective role of autophagy in ESCC and discuss autophagy inhibitors as novel experimental therapeutics to potentiate the effects of anti-cancer therapies and/or to overcome therapeutic resistance in ESCC.