Opportunities and challenges related to ferroptosis in glioma and neuroblastoma

Abstract

A newly identified form of cell death known as ferroptosis is characterized by the peroxidation of lipids in response to iron. Rapid progress in research on ferroptosis in glioma and neuroblastoma has promoted the exploitation of ferroptosis in related therapy. This manuscript provides a review of the findings on ferroptosis-related therapy in glioblastoma and neuroblastoma and outlines the mechanisms involved in ferroptosis in glioma and neuroblastoma. We summarize some recent data on traditional drugs, natural compounds and nanomedicines used as ferroptosis inducers in glioma and neuroblastoma, as well as some bioinformatic analyses of genes involved in ferroptosis. Moreover, we summarize some data on the associations of ferroptosis with the tumor immunotherapy and TMZ drug resistance. Finally, we discuss future directions for ferroptosis research in glioma and neuroblastoma and currently unresolved issues.

Keywords: GPX4; ferroptosis; glioblastoma; immune; neuroblastoma.

Figure 1

Snapshot of ferroptotic pathways. Ferroptosis in GBM is triggered by four main regulatory pathways: iron metabolism, the GPX4 pathway, the FSP1 pathway and lipid metabolism. In iron metabolism, Fe3+ is transported into the cell by TfR1 (transferrin receptor) and subsequently reduced to Fe2+, and some nanoparticles are involved in iron metabolism. The GPX4 pathway is the classic ferroptotic pathway, and the Xc- system plays an important regulatory role in this pathway. p53 is closely related to this pathway. The MDM2-MDMX complex regulates lipid metabolism by altering PPARα activity and ultimately interacts with the FSP1 protein. In lipid metabolism, AA (as well as other PUFAs) is metabolized by ACSL4 and eventually participates in lipid peroxidation. (Created with BioRender).