The overexpression of HIF-1α and HIF-2α as well as the methylation-dependent knockdown of Bcl-2 interacting protein 3 (BNIP3) are associated with the development of sorafenib resistance in HCC, and the demethylation of the BNIP3 promoter can restore BNIP3 expression, suggesting its potential as a molecular target to overcome sorafenib resistance [167]. The gene discussed is BNIP3; the disease is hepatocellular carcinoma.