New research from Memorial Sloan Kettering Cancer Center (MSK) investigates harnessing the power of ferroptosis to spread cell death; reports how an MSK artificial intelligence (AI) model could help improve patient safety; and uses AI to reveal country-specific drivers of global cancer outcomes.
Harnessing the power of ferroptosis to spread cell death
Ferroptosis is a type of cell death that occurs in degenerative conditions and has potential applications in cancer treatment. It is driven by iron-powered lipid damage, which harms cell membranes.
An MSK research team — led by postdoctoral researcher Jyotirekha Das, PhD , and graduate student Saloni Hombalkar , members of the lab of senior study author Michael Overholtzer, PhD — investigated why ferroptosis sometimes kills individual cells and other times spreads as a wave through groups of cells.
They discovered that the spreading type of ferroptosis requires damage to lysosomes — an organelle that recycles cellular waste — and that severe damage causes them to rupture. Enzymes released from lysosomes then help drive necrotic cell rupture. Released iron may additionally amplify damage and potentially affect nearby cells. The scientists also showed that lowering antioxidant defenses, especially by depleting glutathione, shifts cells toward necrosis and enables collective cell death. In contrast, glutathione peroxidase 4 (GPX4) inhibition alone can trigger mixed death types, including apoptosis, which doesn't propagate well.
The findings could help explain tissue damage in conditions like stroke, as well as suggest ways to steer cancer therapy toward propagating, necrotic ferroptosis that may help eliminate resistant tumor cells.
