Effective targeting of PDGFRA-altered high-grade glioma with avapritinib.
Publication/Presentation Date
4-14-2025
Abstract
PDGFRA is crucial to tumorigenesis and frequently genomically altered in high-grade glioma (HGG). In a comprehensive dataset of pediatric HGG (n = 261), we detect PDGFRA mutations and/or amplifications in 15% of cases, suggesting PDGFRA as a therapeutic target. We reveal that the PDGFRA/KIT inhibitor avapritinib shows (1) selectivity for PDGFRA inhibition, (2) distinct patterns of subcellular effects, (3) in vitro and in vivo activity in patient-derived HGG models, and (4) effective blood-brain barrier penetration in mice and humans. Furthermore, we report preliminary clinical real-world experience using avapritinib in pediatric and young adult patients with predominantly recurrent/refractory PDGFRA-altered HGG (n = 8). Our early data demonstrate that avapritinib is well tolerated and results in radiographic response in 3/7 cases, suggesting a potential role for avapritinib in the treatment of HGG with specific PDGFRA alterations. Overall, these translational results underscore the therapeutic potential of PDGFRA inhibition with avapritinib in HGG.
Volume
43
Issue
4
First Page
740
Last Page
756
ISSN
1878-3686
Published In/Presented At
Mayr, L., Neyazi, S., Schwark, K., Trissal, M., Beck, A., Labelle, J., Eder, S. K., Weiler-Wichtl, L., Marques, J. G., de Biagi-Junior, C. A. O., Lo Cascio, C., Chapman, O., Sridhar, S., Kenkre, R., Dutta, A., Wang, S., Wang, J., Hack, O., Nascimento, A., Nguyen, C. M., … Filbin, M. G. (2025). Effective targeting of PDGFRA-altered high-grade glioma with avapritinib. Cancer cell, 43(4), 740–756.e8. https://doi.org/10.1016/j.ccell.2025.02.018
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
40086436
Department(s)
Administration and Leadership
Document Type
Article