Ferroptosis: a promising therapeutic strategy in glioblastoma👇

✅Glioblastoma multiforme (GBM) is an aggressive brain tumor characterized by rapid growth and resistance to conventional therapies. Recent research highlights ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, as a novel and promising approach for GBM treatment.

✅One key mechanism underlying ferroptosis in GBM is glutathione depletion. Inhibition of the cystine/glutamate antiporter system (xCT) limits cystine uptake, leading to reduced glutathione synthesis. As a consequence, the antioxidant enzyme GPX4 becomes inactivated, impairing the cell’s ability to detoxify lipid peroxides.

✅Lipid peroxidation is a central event in ferroptosis. Polyunsaturated fatty acids (PUFAs) incorporated into membrane phospholipids are highly susceptible to oxidative damage. Their conversion into peroxidized phospholipids (PL-PUFA-PE) disrupts membrane integrity and drives lethal oxidative stress.

✅Iron metabolism further amplifies ferroptotic signaling in GBM cells. Elevated intracellular iron, particularly the Fe²⁺ pool, catalyzes redox reactions that generate reactive oxygen species (ROS). This iron-driven ROS production accelerates lipid peroxidation and pushes tumor cells toward ferroptotic death.

✅Collectively, glutathione depletion, GPX4 inactivation, uncontrolled lipid peroxidation, and dysregulated iron metabolism converge to induce ferroptosis. Targeting these interconnected pathways offers a potential strategy to overcome therapy resistance and selectively eliminate GBM cells.

Ferroptosis, a novel form of programmed cell death, offers promising therapeutic potential for drug-resistant glioblastoma multiforme. This review investigates key molecular mediators and emerging strategies targeting ferroptosis, suggesting that its integration with current therapies could improve outcomes for patients with this aggressive brain tumor.