Pladevall-Morera, DavidCastejón-Griñán, MaríaAguilera, PaulaGaardahl, KarinaIngham, AndreasBrosnan-Cashman, Jacqueline AMeeker, Alan KLopez-Contreras, Andres J2023-05-032023-05-032022-03-312072-6694http://hdl.handle.net/10668/20883High-grade glioma, including anaplastic astrocytoma and glioblastoma (GBM) patients, have a poor prognosis due to the lack of effective treatments. Therefore, the development of new therapeutic strategies to treat these gliomas is urgently required. Given that high-grade gliomas frequently harbor mutations in the SNF2 family chromatin remodeler ATRX, we performed a screen to identify FDA-approved drugs that are toxic to ATRX-deficient cells. Our findings reveal that multi-targeted receptor tyrosine kinase (RTK) and platelet-derived growth factor receptor (PDGFR) inhibitors cause higher cellular toxicity in high-grade glioma ATRX-deficient cells. Furthermore, we demonstrate that a combinatorial treatment of RTKi with temozolomide (TMZ)-the current standard of care treatment for GBM patients-causes pronounced toxicity in ATRX-deficient high-grade glioma cells. Our findings suggest that combinatorial treatments with TMZ and RTKi may increase the therapeutic window of opportunity in patients who suffer high-grade gliomas with ATRX mutations. Thus, we recommend incorporating the ATRX status into the analyses of clinical trials with RTKi and PDGFRi.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/ATRXPDGFRiRTKidrug screenglioblastomagliomaresearch article35406561open access10.3390/cancers14071790PMC8997088https://www.mdpi.com/2072-6694/14/7/1790/pdf?version=1648785333https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997088/pdf