Journal Article

DKFZ-2025-00771

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Effective targeting of PDGFRA-altered high-grade glioma with avapritinib.

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. ; Castellani, S. ; Rozowsky, J. S. ; Groves, A. ; Panditharatna, E. ; Cruzeiro, G. A. V. ; Haase, R. D. ; Tabatabai, K. ; Madlener, S. ; Wadden, J. ; Adam, T. ; Kong, S. ; Miclea, M. ; Patel, T. ; Bruckner, K. ; Senfter, D. ; Lämmerer, A. ; Supko, J. ; Guntner, A. S. ; Palova, H. ; Neradil, J. ; Stepien, N. ; Lötsch-Gojo, D. ; Berger, W. ; Leiss, U. ; Rosenmayr, V. ; Dorfer, C. ; Dieckmann, K. ; Peyrl, A. ; Azizi, A. A. ; Baumgartner, A. ; Slaby, O. ; Pokorna, P. ; Clark, L. M. ; Cameron, A. ; Nguyen, Q.-D. ; Wakimoto, H. ; Dubois, F. ; Greenwald, N. F. ; Bandopadhayay, P. ; Beroukhim, R. ; Ligon, K. ; Kramm, C. ; Bronsema, A. ; Bailey, S. ; Stucklin, A. G. ; Mueller, S. ; Skrypek, M. ; Martinez, N. ; Bowers, D. C. ; Jones, D.DKFZ* ; Jones, C. ; Jäger, N.DKFZ* ; Sterba, J. ; Müllauer, L. ; Haberler, C. ; Kumar-Sinha, C. ; Chinnaiyan, A. ; Mody, R. ; Chavez, L. ; Furtner, J. ; Koschmann, C. ; Gojo, J. ; Filbin, M. G.

2025
Cell Press Cambridge, Mass.

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.ccell.2025.02.018

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.

Keyword(s): PDGFRA alteration ; PDGFRA amplification ; PDGFRA inhibitor ; PDGFRA mutation ; avapritinib ; brain penetrance ; diffuse midline glioma ; glioblastoma ; high-grade glioma ; tyrosine kinase inhibitor

Note: 2025 Apr 14;43(4):740-756.e8

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Contributing Institute(s):

1. Pädiatrische Gliomforschung (B360)
2. B062 Pädiatrische Neuroonkologie (B062)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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