We thank the reviewer for this question. Indeed, the sorafenib dose used in this study proved to be slightly more efficacious than TTFields in controlling tumor fold increase. Nevertheless, these differences between the monotherapies, did not reach statistical significance. In accordance, there was no statistical difference between the monotherapies in the expression levels of the LC3 marker and the levels of cleaved PARP. In order to better understand the mechanism of action, we have added experiments to better characterize the autophagy-apoptosis interplay for treatment with concomitant TTFields and sorafenib, which are described in response 3. Of note, the clinical development of TTFields does not aim to replace sorafenib with TTFields, but rather to add TTFields on top of sorafenib and therefore this work focused mainly on the potential added value in combining these 2 modalities.
These examinations were performed for the combined treatment as compared to TTFields and sorafenib alone.