Ferroptosis in glioma therapy: advancements in sensitizing strategies and the complex tumor-promoting roles

Abstract

Ferroptosis, an iron-dependent form of non-apoptotic regulated cell death, is induced by the accumulation of lipid peroxides on cellular membranes. Over the past decade, ferroptosis has emerged as a crucial process implicated in various physiological and pathological systems. Positioned as an alternative modality of cell death, ferroptosis holds promise for eliminating cancer cells that have developed resistance to apoptosis induced by conventional therapeutics. This has led to a growing interest in leveraging ferroptosis for cancer therapy across diverse malignancies. Gliomas are tumors arising from glial or precursor cells, with glioblastoma (GBM) being the most common malignant primary brain tumor that is associated with a dismal prognosis. This review provides a summary of recent advancements in the exploration of ferroptosis-sensitizing methods, with a specific focus on their potential application in enhancing the treatment of gliomas. In addition to summarizing the therapeutic potential, this review also discusses the intricate interplay of ferroptosis and its potential tumor-promoting roles within gliomas. Recognizing these dual roles is essential, as they could potentially complicate the therapeutic benefits of ferroptosis. Exploring strategies aimed at circumventing these tumor-promoting roles could enhance the overall therapeutic efficacy of ferroptosis in the context of glioma treatment.

Keywords: Ferroptosis; Ferroptosis-sensitizing methods; Glioblastoma; Glioma; Neuroinflammation; Regulated cell death.