Understanding the role of autophagy in cancer formation and progression is a real opportunity to treat and cure human cancers

The malignant transformation of a cell produces the accumulation of several cellular adaptions. These changes determine variations in biological processes that are necessary for a cancerous cell to survive during stressful conditions. Autophagy is the main nutrient recycling and metabolic adaptor mechanism in eukaryotic cells, represents a continuous source of energy and biomolecules, and is fundamental to preserve the correct cellular homeostasis during unfavorable conditions. In recent decades, several findings demonstrate a close relationship between autophagy, malignant transformation, and cancer progression. The evidence suggests that autophagy in the cancer context has a bipolar role (it may act as a tumor suppressor and as a mechanism of cell survival for established tumors) and demonstrates that the targeting of autophagy may represent novel therapeutic opportunities. Accordingly, the modulation of autophagy has important clinical benefits in patients affected by diverse cancer types. Currently, about 30 clinical trials are actively investigating the efficacy of autophagy modulators to enhance the efficacy of cytotoxic chemotherapy treatments. A deeper understanding of the molecular pathways regulating autophagy in the cancer context will provide new ways to target autophagy for improving the therapeutic benefits. Herein, we describe how autophagy participates during malignant transformation and cancer progression, and we report the ultimate efforts to translate this knowledge into specific therapeutic approaches to treat and cure human cancers.