A fistful of iron: ferritin as a vulnerability point of the brain cancers

Iron metabolism is increasingly recognized as a key player in the development and progression of various cancers. Iron is required for vital cellular processes such as energy production; however, it can also interact with reactive oxygen species to cause cellular toxicity. Consequently, a host of proteins coordinate iron homeostasis, and ferritin stands out as a promising therapeutic target due to its pivotal role in buffering cellular iron levels. This review explores the relevance of ferritin in brain cancers, shedding light on how it influences the biology of both tumor cells and cancer stem cells (CSCs), a population of tumor cells that is notable in their resistance to conventional treatment strategies. Ferritin plays a critical role in protecting against oxidative stress and boosting resistance to ferroptosis, a form of cell death often evaded by CSCs. Development of cutting-edge strategies designed to target ferritin, including ferritinophagy-inducing compounds and novel redox-based therapies that can capitalize on the iron dependency of CSCs is discussed in context. We propose that the iron addiction of brain cancer cells provides a specific susceptibility, whereby removing their iron buffering mechanism via targeting of ferritin can result in favorable treatment outcomes, including the induction of iron-dependent cell death. Future studies on the modulation of ferritin offer a ground-breaking therapeutic strategy to undermine CSC-driven tumor growth, overcome resistance to conventional therapies, and ultimately improve treatment outcomes for patients battling brain cancers.