New strategy to improve resistance to low-intensity electric field treatment (TTFields) in brain tumors.

Glioblastomas (GBMs) are highly aggressive brain tumors that almost invariably recur despite standard treatments (surgery, radiotherapy, and chemotherapy). The recent addition of alternating electric fields (TTFields) has improved prognosis, but resistance remains, notably due to glioma stem cells (GSCs), which are known for their resistance to therapies. FGFR receptors play a key role in GBM aggressiveness and in the resistance of GSCs to radiotherapy.

We investigated the effect of FGFR inhibition using pemigatinib (an FGFR1–3 inhibitor) in combination with TTFields. Our study shows that pemigatinib disrupts FGFR signaling and enhances the effect of TTFields by reducing GSC survival and clonogenic capacity. Adding pemigatinib to the TTFields + radiotherapy combination also increases DNA damage. These results suggest that targeting FGFR could enhance the effectiveness of first-line treatments against GBM.

This work has led to the launch of the EXOFIELDS clinical trial at the IUCT-Oncopole, which has already enrolled nearly 40 patients. The trial aims to validate our research and continue identifying new therapeutic targets to optimize the effectiveness of TTFields in the clinical treatment of GBM.

Mains perspectives of this work :

• Clinical trial EXOFIELDS
• Patent : WO2023242825A1 – Compositions and methods for treating with a combination of alternating electric fields and FGF inhibitors – Tali Voloshin-Sela , Lilach Avig-Dor , Anat Klein-Goldberg , Rom Paz , Elizabeth Moyal, Valérie Gouazé-Andersson

Collaborations and partnerships

• Financeurs : Novocure
• Collaboration entre équipes du CRCT et de l’IUCT-Oncopole