Publication: ATRX-Deficient High-Grade Glioma Cells Exhibit Increased Sensitivity to RTK and PDGFR Inhibitors.
Loading...
Identifiers
Date
2022-03-31
Authors
Pladevall-Morera, David
Castejón-Griñán, María
Aguilera, Paula
Gaardahl, Karina
Ingham, Andreas
Brosnan-Cashman, Jacqueline A
Meeker, Alan K
Lopez-Contreras, Andres J
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
High-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.
Description
MeSH Terms
DeCS Terms
CIE Terms
Keywords
ATRX, PDGFRi, RTKi, drug screen, glioblastoma, glioma