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Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV\u2010infected patients due to HBx\u2010related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV\u2010positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV\u2010positive HCC cells and human tissues. This combination therapy disrupts the PI3K\/Akt\/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC\u2010mediated suppression of SOD1 further enhances SF sensitivity in HBV\u2010positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC\u2010SF combination could serve as a promising strategy for overcoming SF resistance in HBV\u2010related HCC, potentially optimizing therapy outcomes.<\/jats:p>","DOI":"10.1111\/jcmm.18533","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:08:02Z","timestamp":1721606882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SOD1 inhibition enhances sorafenib efficacy in HBV\u2010related hepatocellular carcinoma by modulating PI3K\/Akt\/mTOR pathway and ROS\u2010mediated cell death"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-8196","authenticated-orcid":false,"given":"Jooyoung","family":"Lee","sequence":"first","affiliation":[{"name":"Asan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine  Seoul South Korea"},{"name":"Department of Biochemistry and Molecular 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