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EXTH-127. Kinome Shifts Post Tumor Treating Fields Reveal Novel Therapeutic Opportunities in Therapy-Resistant Glioblastoma
Abstract   Open access   Peer reviewed

EXTH-127. Kinome Shifts Post Tumor Treating Fields Reveal Novel Therapeutic Opportunities in Therapy-Resistant Glioblastoma

Taylor Schanel, Amber Jones, Rhea Pandit, Joshua Anderson, Patricia Hicks, Corinne Griguer, Braden McFarland, Christopher Willey and Anita Hjelmeland
Neuro-oncology (Charlottesville, Va.), Vol.27(Supplement_5), pp.v369-v369
11/11/2025
DOI: 10.1093/neuonc/noaf201.1460
PMCID: PMC12601377
url
https://doi.org/10.1093/neuonc/noaf201.1460View
Published (Version of record) Open Access

Abstract

A non-invasive treatment for glioblastoma (GBM) is Tumor Treating Fields (TTFields), which are alternating electrical fields applied through electrodes on the skin. TTFields are approved for the treatment of newly diagnosed GBMs in the adjuvant setting with temozolomide and for recurrent GBMs as a monotherapy. Although TTFields can already improve both progression-free and overall survival, enhancing the efficacy of TTFields would have substantial clinical benefits. To accomplish this goal, we analyzed the effects of TTFields on the kinome of paired GBM cells with and without acquired temozolomide or radio- resistance. We focused on analyzing the kinome to increase clinical translation, because there are many kinase inhibitors that are being clinically tested or already FDA approved. Using a PamStation to measure kinase activity as determined by phosphorylation of known peptide sequences, we predicted the kinases that were activated or repressed by TTFields treatment. We found that TTFields increased PDGFRα activity and decreased CK2α activity in both newly diagnosed and temozolomide-resistant GBM cells. Although we have yet to identify common kinase activity changes upon TTFields treatment of newly diagnosed and irradiation-resistant GBM cells, our data does suggest additional kinases to be explored as either mechanisms of resistance or biomarkers for therapeutic response to TTFields. Importantly, TTFields treatment decreased the growth of both newly diagnosed and temozolomide-resistant or radiation-resistant GBM cells from xenografts. Building from our kinome data, we added a blood brain barrier penetrant PDGFR inhibitor to TTFields therapy. PDGFR inhibition with TTFields treatment significantly decreased the growth of newly diagnosed and temozolomide-resistant GBM cells. Further in vivo testing of TTFields with PDGFR antagonists is warranted as is determining whether PDGFR amplified GBMs are more resistant to TTFields. We will continue to add blood brain barrier penetrant FDA-approved kinase inhibitors towards identified targets to TTFields in order to maximize therapeutic efficacy.

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