Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities

Ferroptosis is a non-apoptotic form of regulated cell death driven by iron dependent lipid peroxidation. It sits at the intersection of several hallmarks of metastatic cancer, including metabolic rewiring, membrane remodeling, epithelial mesenchymal plasticity, immune editing, and adaptation to distant niches. In this review, we integrate biochemical mechanisms with single cell, spatial, and in vivo data to map how ferroptotic pressure changes as tumor cells invade, travel through vessels, extravasate, enter dormancy, and re-awaken to form overt metastases. We highlight that these dynamics are strongly shaped by organ context. Lymph and adipose rich environments buffer lipid peroxidation and favor survival. In…