Similarly, the downregulation of Kelch-like ECH-associated protein 1 (KEAP1) in response to sorafenib administration increased the activity of Nrf2, a key transcription factor controlling antioxidant responses, which contributed to enhance drug resistance to sorafenib, lenvatinib, and regorafenib in HCC [56]. This evidence concerns the gene KEAP1 and hepatocellular carcinoma.