ROS were previously shown to play a role in lenvatinib-mediated anti-tumor effects in HUH7 cells, and their accumulation by lenvatinib, as well as by sorafenib and regorafenib, was associated with Keap1-mediated downregulation of Nrf2, a transcription factor playing a key role in the control of antioxidant responses (53). The gene discussed is KEAP1; the disease is neoplasm.