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2 Molecular mechanisms of ferroptosis in melanoma and its immunomodulatory functions Melanoma is one of the most aggressive cutaneous malignancies with high metastatic potential and poor prognosis, especially in advanced stages where conventional therapies and immunotherapies often face limitations due to intrinsic or acquired resistance ( 2.1 Core biochemical pathways of ferroptosis and their regulation in melanoma Ferroptosis is a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation (LPO), fundamentally driven by the loss of activity of glutathione peroxidase 4 (GPX4), which normally detoxifies lipid hydroperoxides ( Melanoma cells exhibit remarkable metabolic plasticity to resist ferroptosis

Cocking, C., Walton, J., Kehoe, L., Cashman, K

It has been proposed that deficiency of intracellular cysteine induces ferroptosis primarily due to failure to synthesize GSH, which protects cells against ROS and lipid peroxidation 18

GABA-A receptors are chloride channels that in response to GABA binding increases chloride influx into the neuron

10.1172/JCI4106 240