AUTHOR=Parik Sweta , Fernández-García Juan , Lodi Francesca , De Vlaminck Karen , Derweduwe Marleen , De Vleeschouwer Steven , Sciot Raf , Geens Wietse , Weng Linqian , Bosisio Francesca Maria , Bergers Gabriele , Duerinck Johnny , De Smet Frederick , Lambrechts Diether , Van Ginderachter Jo A. , Fendt Sarah-Maria TITLE=GBM tumors are heterogeneous in their fatty acid metabolism and modulating fatty acid metabolism sensitizes cancer cells derived from recurring GBM tumors to temozolomide JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.988872 DOI=10.3389/fonc.2022.988872 ISSN=2234-943X 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.