Iron metabolism: a double-edged sword in the resistance of glioblastoma to therapies

• Role of cellular iron metabolism in the progression of GBM and resistance to therapies.
• Recent trends in targeting iron signaling and the modulation of iron protein-partner expression.
• Importance of iron metabolism for the application of drugs and nanomedicines to GBM treatment.

Glioblastoma (GBM), the deadliest primary tumor of the central nervous system (CNS), is a clear illustration of the resistance of cancer cells to conventional therapies. Application of combinatorial strategies able to overcome pivotal factors of GBM resistance, particularly within the resection margins, represents an essential issue. This review focuses on the role of iron metabolism in GBM progression and resistance to therapy, and the impact of its pharmaceutical modulation on the disease. Iron, through its involvement in many biological processes, is a key factor in the control of cell behavior and cancer biology. Therefore, targeting cellular iron signaling or taking advantage of its dysregulation in cancer cells may lead to new opportunities for improving treatments and drug delivery in GBM.