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TMET-33. Systemic Cyst(e)inase administration induces Ferroptosis and synergizes with Temozolomide in Glioblastoma

Year: 2025

Type: conference-abstract

Abstract: Glioblastoma (GBM), an aggressive primary brain cancer, exhibits therapeutic resistance because of tumor heterogeneity and highly plastic glioma stem cells (GSCs). This study targets the metabolic vulnerability of GSCs to cysteine depletion using Cyst(e)inase, a cysteine-degrading enzyme. In patient-derived GSCs and orthotopic xenograft murine models, Cyst(e)inase inhibited GSC growth and extended animal survival by inducing ferroptosis. Mechanistically, Cyst(e)inase triggered elevated reactive oxygen species, glutathione depletion, and lipid peroxidation, indicative of ferroptosis. Critically, Cyst(e)inase synergized with temozolomide (TMZ), the standard GBM chemotherapy, markedly enhancing its efficacy even in TMZ-resistant xenografts. These findings establish cysteine metabolism as a promising therapeutic target in GBM and position Cyst(e)inase, particularly in combination with TMZ, as a promising therapeutic strategy.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/noaf201.1724

Authors: Fahim Ahmad, Blair Rendina, Chixiang Chen, Haoyu Ren, Christine Brantner, Tijana Dukic, Delmar Miles, Jeffrey Winkles, Graeme Woodworth, Sarita Bhetawal, Everett Stone, Eli Bar

Institutions: University of Maryland, Baltimore, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore County, The University of Texas at Austin

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W4416140207

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