Samples from control and TTFields treated conditions. In Various cell lines under different time points.

Tumor Treating Fields (TTFields) therapy is an approved cancer treatment modality, based on non-invasive application of electric fields to the tumor region. Proteomic and cell biology methods revealed a versatile mechanism of action to be involved in the response to TTFields. In the current research we performed whole transcriptome analysis across tumor types to identify pan-cancer responses to TTFields. The transcriptomic analysis supported previous reported effects: downregulation of pathways associated with cell cycle, cell growth, and proliferation; downregulation of DNA replication and DNA repair pathways; and upregulation of cellular responses to stress – senescence, autophagy, and apoptosis. Notably, the transcriptomic analysis identified previously unrecognized downstream effects of TTFields on cellular metabolism, with downregulation of protein and RNA metabolism, and upregulation of steroid biosynthesis. Importantly, this study revealed similar response patterns to TTFields across different tumor types. Overall, the results align with already pinpointed mechanisms for the response to TTFields and reveal new avenues for mechanistic investigation.