The crosstalk between autophagy and ferroptosis: what can we learn to target drug resistance in cancer?

Autophagy is a conserved intracellular degradation system that plays a dual role in cell death; thus, therapies targeting autophagy in cancer are somewhat controversial. Ferroptosis is a new form of regulated cell death featured with the iron-dependent accumulation of lethal lipid ROS. This pathway is morphologically, biochemically and genetically distinct from other forms of cell death. Accumulating studies have revealed crosstalk between autophagy and ferroptosis at the molecular level. In this review, we summarize the mechanisms of ferroptosis and autophagy, and more importantly, their roles in the drug resistance of cancer. Numerous connections between ferroptosis and autophagy have been revealed, and a strong causal relationship exists wherein one process controls the other and can be utilized as potential therapeutic targets for cancer. The elucidation of when and how to modulate their crosstalk using therapeutic strategies depends on an understanding of the fine-tuned switch between ferroptosis and autophagy, and approaches designed to manipulate the intensity of autophagy might be the key. Copyright 2019 Cancer Biology & Medicine.