Fig. 6. Schematic summary of targeting autophagy for RB therapy.

Persistent cells are a small subgroup of cancer cells that remain viable under carboplatin treatment, leading to multidrug resistance by increasing autophagy activity. Up-regulated autophagy inhibits caspase-mediated apoptosis, but increases the sensitivity of drug-resistant RB cells to ferroptosis. In particular, 4-octyl itaconate activates NCOA4-mediated ferritinophagy, leading to ferritin degradation and subsequent free iron accumulation, and finally oxidative damage through the iron-mediated ROS production via Fenton reaction.