1. GBM tumors are heterogeneous in their fatty acid metabolism and modulating fatty acid metabolism sensitizes cancer cells derived from recurring GBM tumors to temozolomide
- Author
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Sweta Parik, Juan Fernández-García, Francesca Lodi, Karen De Vlaminck, Marleen Derweduwe, Steven De Vleeschouwer, Raf Sciot, Wietse Geens, Linqian Weng, Francesca Maria Bosisio, Gabriele Bergers, Johnny Duerinck, Frederick De Smet, Diether Lambrechts, Jo A. Van Ginderachter, Sarah-Maria Fendt, Brussels Heritage Lab, Department of Bio-engineering Sciences, Faculty of Sciences and Bioengineering Sciences, Cellular and Molecular Immunology, Clinical sciences, Laboratory for Medical and Molecular Oncology, Surgical clinical sciences, Faculty of Medicine and Pharmacy, Neurosurgery, and Neuroprotection & Neuromodulation
- Subjects
Cancer Research ,Science & Technology ,glioblastoma ,INHIBITION ,DEATH ,lipotoxicity ,VIABILITY ,LIpotoxicity ,surgery ,FERROPTOSIS ,GRADE ,Oncology ,fatty acid metabolism ,MARKER ,tumor heterogeneity ,FADS2 ,Life Sciences & Biomedicine ,SCD1 - Abstract
Glioblastoma is a highly lethal grade of astrocytoma with very low median survival. Despite extensive efforts, there is still a lack of alternatives that might improve these prospects. We uncovered that the chemotherapeutic agent temozolomide impinges on fatty acid synthesis and desaturation in newly diagnosed glioblastoma. This response is, however, blunted in recurring glioblastoma from the same patient. Further, we describe that disrupting cellular fatty acid homeostasis in favor of accumulation of saturated fatty acids such as palmitate synergizes with temozolomide treatment. Pharmacological inhibition of SCD and/or FADS2 allows palmitate accumulation and thus greatly augments temozolomide efficacy. This effect was independent of common GBM prognostic factors and was effective against cancer cells from recurring glioblastoma. In summary, we provide evidence that intracellular accumulation of saturated fatty acids in conjunction with temozolomide based chemotherapy induces death in glioblastoma cells derived from patients. ispartof: FRONTIERS IN ONCOLOGY vol:12 ispartof: location:Switzerland status: published
- Published
- 2022