Reactive oxygen species regulation of autophagy in cancer: Implications for cancer treatment

Reactive oxygen species (ROS) are important in regulating normal cellular processes, but deregulated ROS contribute to the development of various human diseases including cancers. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and upregulated in response to intracellular ROS or extracellular oxidative stress. This leads to selective lysosomal self-digestion of intracellular components to maintain cellular homeostasis. Hence, autophagy is the survival pathway, conferring stress adaptation and promoting viability under oxidative stress. However, increasing evidence has demonstrated that autophagy can also lead to cell death under oxidative stress conditions. In addition, altered autophagic signaling pathways that lead to decreased autophagy are frequently found in many human cancers. This review discusses the advances in understanding of the mechanisms of ROS-induced autophagy and how this process relates to tumorigenesis and cancer therapy.

► Reactive oxygen species (ROS) induce autophagy.
► ROS induce autophagy through regulation of mTOR-dependent and -independent signaling pathways.
► Autophagy could contribute to both cell survival and cell death under oxidative stress.
► Altered autophagy contributes to both cancer suppression and cancer progression involving ROS.
► Targeted cancer therapeutics could regulate autophagy toward cell survival or cell death mediated by ROS.