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Review
. 2022 Feb 20;58(2):319.
doi: 10.3390/medicina58020319.

Ferroptosis Involvement in Glioblastoma Treatment

Andrei-Otto Mitre  1 , Alexandru Ioan Florian  2   3 , Andrei Buruiana  4 , Armand Boer  1 , Ioana Moldovan  1 , Olga Soritau  5 , Stefan Ioan Florian  2   3 , Sergiu Susman  1   6
Affiliations
Review

Ferroptosis Involvement in Glioblastoma Treatment

Andrei-Otto Mitre et al. Medicina (Kaunas). .

Abstract

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors. Current standard therapy includes tumor resection surgery followed by radiotherapy and chemotherapy. Due to the tumors invasive nature, recurrences are almost a certainty, giving the patients after diagnosis only a 12-15 months average survival time. Therefore, there is a dire need of finding new therapies that could potentially improve patient outcomes. Ferroptosis is a newly described form of cell death with several implications in cancer, among which GBM. Agents that target different molecules involved in ferroptosis and that stimulate this process have been described as potentially adjuvant anti-cancer treatment options. In GBM, ferroptosis stimulation inhibits tumor growth, improves patient survival, and increases the efficacy of radiation and chemotherapy. This review provides an overview of the current knowledge regarding ferroptosis modulation in GBM.

Keywords: cell death; ferroptosis; glioblastoma; lipid peroxidation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The ferroptosis pathway. (A): the xCT-cysteine pathway; (B): the iron pathway; (C): the PUFA and lipid peroxidation pathway; (D): the GPX4 involvement. Abbreviations: ACSL4, long-chain-fatty-acid-CoA ligase 4; Cys, cysteine; DMT1, divalent metal transporter 1; Fe, iron; γ-GCS, γ-glutamylcysteine synthetase; γ-glutamylcys, γ-glutamylcysteine; Glu, glutamate; GPX4, glutathione peroxidase 4; GS, glutathione synthetase; GSH, glutathione; GSSG, glutathione disulphide; LOH, lipid alcohol; LOOH, lipid peroxide; LOX, lipoxygenase; LPCAT3, lysophosphatidylcholine acyltransferase 3; PE, phosphatidylethanolamine; PUFA, polyunsaturated fatty acids; SLC3A2, solute carrier family 3 member 2; SLC7A11, solute carrier family 7 member 11; STEAP3, six-transmembrane epithelial antigen of the prostate 3; TFR1, transferrin receptor 1; xCT, cystine/glutamate antiporter.
Figure 2
Figure 2
Ferroptosis modulation in glioblastoma. Abbreviations: DMT1, divalent metal transporter 1; GPX4, glutathione peroxidase 4; PCBP2, poly(rC)-binding protein 2; STEAP3, six-transmembrane epithelial antigen of the prostate 3; TFR, transferrin receptor; TMZ, temozolomide; xCT, cystine/glutamate antiporter.
See this image and copyright information in PMC

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