January 2026 - Lisa Mayr

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Dr. Lisa Mayr

MedUni Wien RESEARCHER OF THE MONTH January 2026

PDGFRA is essential for tumorigenesis and thus frequently genomically altered in pediatric high-grade glioma (HGG). In a comprehensive dataset of pediatric HGG (n = 261), we detected 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.

Selected Literature

1. Mayr L, Neyazi S, Schwark K, Trissal M, Beck A, Labelle J, Eder SK, Weiler-Wichtl L, Marques JG, de Biagi-Junior CAO, Lo Cascio C, Chapman O, Sridhar S, Kenkre R, Dutta A, Wang S, Wang J, Hack O, Nascimento A, Nguyen CM, Castellani S, Rozowsky JS, Groves A, Panditharatna E, Cruzeiro GAV, Haase RD, Tabatabai K, Madlener S, Wadden J, Adam T, Kong S, Miclea M, Patel T, Bruckner K, Senfter D, Lämmerer A, Supko J, Guntner AS, Palova H, Neradil J, Stepien N, Lötsch-Gojo D, Berger W, Leiss U, Rosenmayr V, Dorfer C, Dieckmann K, Peyrl A, Azizi AA, Baumgartner A, Slaby O, Pokorna P, Clark LM, Cameron A, Nguyen QD, Wakimoto H, Dubois F, Greenwald NF, Bandopadhayay P, Beroukhim R, Ligon K, Kramm C, Bronsema A, Bailey S, Stucklin AG, Mueller S, Skrypek M, Martinez N, Bowers DC, Jones DTW, Jones C, Jäger N, Sterba J, Müllauer L, Haberler C, Kumar-Sinha C, Chinnaiyan A, Mody R, Chavez L, Furtner J, Koschmann C, Gojo J, Filbin MG. Effective targeting of PDGFRA-altered high-grade glioma with avapritinib. Cancer Cell. 2025 Apr 14;43(4):740-756.e8. doi: 10.1016/j.ccell.2025.02.018. Epub 2025 Mar 13. PMID: 40086436; PMCID: PMC12121847.

2. Sevelda F, Mayr L, Kubista B, Lötsch D, van Schoonhoven S, Windhager R, Pirker C, Micksche M, Berger W. EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance. J Exp Clin Cancer Res. 2015 Nov 2;34:134. doi: 10.1186/s13046-015-0251-5. PMID: 26526352; PMCID: PMC4630894.

3. Kubista B, Schoefl T, Mayr L, van Schoonhoven S, Heffeter P, Windhager R, Keppler BK, Berger W. Distinct activity of the bone-targeted gallium compound KP46 against osteosarcoma cells - synergism with autophagy inhibition. J Exp Clin Cancer Res. 2017 Apr 12;36(1):52. doi: 10.1186/s13046-017-0527-z. PMID: 28403890; PMCID: PMC5389188.

4. Mayr L, Pirker C, Lötsch D, Van Schoonhoven S, Windhager R, Englinger B, Berger W, Kubista B. CD44 drives aggressiveness and chemoresistance of a metastatic human osteosarcoma xenograft model. Oncotarget. 2017 Dec 9;8(69):114095-114108. doi: 10.18632/oncotarget.23125. PMID: 29371972; PMCID: PMC5768389.

5. Gojo J, Pavelka Z, Zapletalova D, Schmook MT, Mayr L, Madlener S, Kyr M, Vejmelkova K, Smrcka M, Czech T, Dorfer C, Skotakova J, Azizi AA, Chocholous M, Reisinger D, Lastovicka D, Valik D, Haberler C, Peyrl A, Noskova H, Pál K, Jezova M, Veselska R, Kozakova S, Slaby O, Slavc I, Sterba J. Personalized Treatment of H3K27M-Mutant Pediatric Diffuse Gliomas Provides Improved Therapeutic Opportunities. Front Oncol. 2020 Jan 10;9:1436. doi: 10.3389/fonc.2019.01436. PMID: 31998633; PMCID: PMC6965319.

6. Mayr L, Guntner AS, Madlener S, Schmook MT, Peyrl A, Azizi AA, Dieckmann K, Reisinger D, Stepien NM, Schramm K, Laemmerer A, Jones DTW, Ecker J, Sahm F, Milde T, Pajtler KW, Blattner-Johnson M, Strbac M, Dorfer C, Czech T, Kirchhofer D, Gabler L, Berger W, Haberler C, Müllauer L, Buchberger W, Slavc I, Lötsch-Gojo D, Gojo J. Cerebrospinal Fluid Penetration and Combination Therapy of Entrectinib for Disseminated ROS1/NTRK-Fusion Positive Pediatric High-Grade Glioma. J Pers Med. 2020 Dec 18;10(4):290. doi: 10.3390/jpm10040290. PMID: 33353026; PMCID: PMC7766483.

7. Mayr L, Gojo J, Peyrl A, Azizi AA, Stepien NM, Pletschko T, Czech T, Dorfer C, Lambo S, Dieckmann K, Haberler C, Kool M, Slavc I. Potential Importance of Early Focal Radiotherapy Following Gross Total Resection for Long-Term Survival in Children With Embryonal Tumors With Multilayered Rosettes. Front Oncol. 2020 Dec 17;10:584681. doi: 10.3389/fonc.2020.584681. PMID: 33392079; PMCID: PMC7773839.

8. Liu I, Jiang L, Samuelsson ER, Marco Salas S, Beck A, Hack OA, Jeong D, Shaw ML, Englinger B, LaBelle J, Mire HM, Madlener S, Mayr L, Quezada MA, Trissal M, Panditharatna E, Ernst KJ, Vogelzang J, Gatesman TA, Halbert ME, Palova H, Pokorna P, Sterba J, Slaby O, Geyeregger R, Diaz A, Findlay IJ, Dun MD, Resnick A, Suvà ML, Jones DTW, Agnihotri S, Svedlund J, Koschmann C, Haberler C, Czech T, Slavc I, Cotter JA, Ligon KL, Alexandrescu S, Yung WKA, Arrillaga-Romany I, Gojo J, Monje M, Nilsson M, Filbin MG. The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location. Nat Genet. 2022 Dec;54(12):1881-1894. doi: 10.1038/s41588-022-01236-3. Epub 2022 Dec 5. PMID: 36471067; PMCID: PMC9729116.

9. Neftel C, Laffy J, Filbin MG, Hara T, Shore ME, Rahme GJ, Richman AR, Silverbush D, Shaw ML, Hebert CM, Dewitt J, Gritsch S, Perez EM, Gonzalez Castro LN, Lan X, Druck N, Rodman C, Dionne D, Kaplan A, Bertalan MS, Small J, Pelton K, Becker S, Bonal D, Nguyen QD, Servis RL, Fung JM, Mylvaganam R, Mayr L, Gojo J, Haberler C, Geyeregger R, Czech T, Slavc I, Nahed BV, Curry WT, Carter BS, Wakimoto H, Brastianos PK, Batchelor TT, Stemmer-Rachamimov A, Martinez-Lage M, Frosch MP, Stamenkovic I, Riggi N, Rheinbay E, Monje M, Rozenblatt-Rosen O, Cahill DP, Patel AP, Hunter T, Verma IM, Ligon KL, Louis DN, Regev A, Bernstein BE, Tirosh I, Suvà ML. An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. Cell. 2019 Aug 8;178(4):835-849.e21. doi: 10.1016/j.cell.2019.06.024. Epub 2019 Jul 18. PMID: 31327527; PMCID: PMC6703186.