Autophagy-dependent ferroptosis as a therapeutic target in cancer.

Ferroptosis is an iron-dependent form of cell death associated with the accumulation of labile iron and cytotoxic lipid peroxides. Increasing evidence reveals that ferroptosis is not a self-standing phenomenon and has close connections with other cellular events. Remarkably, recent insights show that ferroptosis is dependent on autophagy, which is a lysosomal degradation pathway responsible for the recycling of damaged cellular components under survival stress. Autophagy is capable of contributing to ferroptosis through degradation of the ferritin, an iron-storage protein, accompanied with the accumulation of iron levels and lipid ROS. The interplay between autophagy and ferroptosis also reveals emerging opportunities for novel tumor therapies, which has inspired the development of many treatment strategies capable of inducing ferroptosis in tumor cells via autophagic pathways based on molecular and nanoparticulate agents. In this review, we summarize the specific molecular and regulatory networks of autophagy-dependent ferroptosis and highlight their pathophysiological impact on various aspects of tumor cells. A perspective was also provided regarding the preliminary therapeutic exploitation of ferroptosis/autophagy crosstalk for tumor treatment.