KEAP1 and hepatocellular carcinoma: Firstly, as KEAP1 loss mediates sorafenib, lenvatinib, and ragorafenib resistance, we suggest that patients with HCC that are resistant to first-line treatment with sorafenib, if mediated by KEAP1 loss-of-function, will not respond to second-line treatment with lenvatinib or ragorafenib (and vice-versa).