Electrothermal decoupling for investigating tumor treating fields of glioblastoma

Objective.Tumor treating fields (TTFields), a non-invasive cancer therapy employing low-intensity alternating electric fields to inhibit cancer cell division, has been used to treat glioblastoma (GBM). While clinically established for GBM, the biological contribution of the intrinsic mild hyperthermia (iMH) remains not fully elucidated, limiting mechanistic clarity and treatment optimization.Approach.This study presents a precisionin vitroplatform designed to decouple the electrical and thermal components of TTFields (230 kHz, 2 V cm^-1). Based on numerical simulations, the platform utilizes a defined monitoring area to ensure field uniformity and an active thermodynamic compensation protocol to isolate electric and thermal modalities.Main results.Results indicated that the electric field primarily inhibited cell proliferation (32.0% reduction) and migration, whereas the iMH was the primary mediator of cytotoxicity and apoptosis. Notably, the combined electrothermal treatment exhibited a synergistic anti-tumor effect exceeding the additive effects of individual modalities.Significance.These findings suggest that the iMH component of TTFields functions as a therapeutic sensitizer rather than a side effect, offering a basis for optimizing future GBM treatment strategies.