The functional role of ferroptosis in the development and progression of common cancers

Ferroptosis is a recently characterised, iron-dependent form of regulated cell death governed by the interplay between iron homeostasis, antioxidant defence systems, the accumulation of reactive oxygen species (ROS), and lipid peroxidation. It has been hypothesised that impaired induction of ferroptosis may play a role in the initiation and progression of multiple malignancies, including, but not limited to, lung, gastric, breast, and colorectal cancers, as well as leukemia, ovarian, liver, pancreatic, and prostate cancers. Emerging evidence highlights the pivotal roles of lipid metabolism, iron regulation, and oxidative stress responses in modulating cancer cells' susceptibility to ferroptotic death. Key molecular regulators, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4), have been identified as playing essential roles in orchestrating this process. Furthermore, the tumour microenvironment and oncogenic signalling pathways have been demonstrated to exert a substantial influence on ferroptosis sensitivity. Elucidation of the mechanistic roles of ferroptosis in cancer biology has the potential to facilitate the discovery of novel biomarkers and therapeutic targets. This review synthesises current advances in our understanding of ferroptosis regulation within the most common human cancers.