Progress in Research on the Mechanisms and Therapeutic Strategies of SLC7A11 Regulation in Glioma

Sep 30, 2026

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This review summarizes the critical role of SLC7A11 in glioma pathogenesis and its value as a therapeutic target. By mediating cystine uptake and glutamate release, SLC7A11 supports glutathione (GSH) synthesis, protecting glioma cells from oxidative stress and sustaining antioxidant defenses. Elevated SLC7A11 correlates with higher malignancy grade and poorer prognosis, while high expression is linked to resistance to radiotherapy and chemotherapy. Inhibiting SLC7A11 reduces GSH, increases ROS accumulation, and triggers ferroptosis. The review also highlights upstream regulators and therapeutic targeting strategies.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

1 Introduction

Glioma classification and ferroptosis sensitivity

IDH-mutant versus IDH-wild-type gliomas

Review scope and significance

SLC7A11 in antioxidant defense and tumor progression

Therapeutic implications of targeting SLC7A11

Wei et al. Discover Oncology (2026) 17:25 [https://doi.org/10.1007/s12672-025-04154-y](https://doi.org/10.1007/s12672-025-04154-y) Discover Oncology REVIEW Open Access Progress in research on the mechanismsand therapeutic strategies of SLC7A11 regulation in glioma Qianfeng Wei 1†, Bangfa Xiong 1†, Guangming Yang 1, Jiahui Wang 1 and Erqing Chai 1,2* †Wei Qianfeng and Xiong Bangfa have contributed equally. *Correspondence: Erqing Chai [1453583455@qq.com](1453583455@qq.com) 1The First School Of Clinical Medical of Gansu University of Chinese Medicine, Lanzhuo 730099, China 2Present address: Cerebrovascular Disease Centre, Disease of Gansu Province, Key Laboratory of Cerebrovascular , Gansu Provincial Hospital , Lanzhuo 730099, China Abstract This review summarizes the critical role of SLC7A11 in the pathogenesis of glioma and its potential as a therapeutic target. By mediating cystine uptake and glutamate release, SLC7A11 promotes glutathione (GSH) synthesis, protecting glioma cells from oxidative stress-induced damage and maintaining the antioxidant defense mechanisms. Its expression levels are closely correlated with glioma malignancy and prognosis, with significantly elevated expression observed in high-grade gliomas, suggesting its involvement in malignant progression. Therapeutically, high SLC7A11 expression is associated with resistance to radiotherapy and chemotherapy, making it an attractive target. Studies have shown that inhibiting SLC7A11 function (e. g., using sulfasalazine) reduces GSH synthesis, induces reactive oxygen species (ROS) accumulation, and triggers ferroptosis in glioma cells. Furthermore, molecules such asp53, p62, and OTUB1 regulate SLC7A11 expression, influencing glioma development. Therapeutic strategies targeting SLC7A11, including the application of inhibitors and exploration of molecular targets, offer novel directions for glioma treatment. Keywords Glioma, SLC7A11, Ferroptosis, GSH 1 Introduction Gliomas, which originate from the brain’s neuroglial cells, are the most common primary malignant intracranial tumors [1]. In IDH-mutant gliomas, SLC7A11 expression is relatively low, leading to a higher sensitivity to ferroptosis. This may be because IDH mutations affect cellular metabolism and antioxidant capacity, thereby altering the regulatory mechanisms and functions of SLC7A11. In contrast, SLC7A11 expression is higher in IDH-wild-type gliomas, making them more resistant to ferroptosis and promoting malignant tumor progression [2]. Based on the WHO’s central nervous system tumor classification, gliomas are graded from I to IV. Grades I and II are low-grade gliomas, with slow growth and low malignancy, whereas grades III and IV are high-grade gliomas, featuring rapid cell proliferation, invasiveness, and poor prognosis [1, 3–5]. Pediatric and adult gliomas differ in SLC7A11 expression patterns and ferroptosis regulation. Pediatric gliomas may be influenced by developmentally specific signaling pathways. © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence

FAQs

How does SLC7A11 influence glioma cell survival?

SLC7A11 mediates cystine uptake and glutamate release to promote glutathione (GSH) synthesis. This enhances the antioxidant defense system and protects glioma cells from oxidative stress.

Why is SLC7A11 considered a promising therapeutic target?

High SLC7A11 expression is associated with worse malignancy grade and prognosis, and it is linked to resistance to radiotherapy and chemotherapy. Inhibiting its function reduces GSH, increases ROS, and can trigger ferroptosis.

What evidence is discussed regarding ferroptosis in relation to SLC7A11?

The review explains that SLC7A11 supports antioxidant capacity and thereby affects ferroptosis sensitivity. It also notes that ferroptosis is a regulated, iron- and lipid-peroxidation–dependent cell death process and may be relevant to multiple diseases.

Sep 30, 2026

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