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This combination therapy involves high-dose intravenous ascorbic acid (Vitamin C) administered in conjunction with sorafenib for the treatment of metastatic hepatocellular carcinoma. Investigated in a Phase I/II clinical trial (NCT04033107) sponsored by Thomas Jefferson University, the regimen utilizes pharmacologic doses of ascorbic acid (75 grams) to act as a pro-oxidant. At these concentrations, ascorbic acid generates hydrogen peroxide, which selectively induces oxidative stress and apoptosis in cancer cells. Sorafenib is a multi-kinase inhibitor that targets the Raf/MEK/ERK pathway and receptor tyrosine kinases involved in angiogenesis, such as VEGFR and PDGFR. Preclinical studies suggest that the combination of these two agents results in synergistic anti-tumor activity through the dysregulation of cellular calcium homeostasis and mitochondrial dysfunction, potentially enhancing the efficacy of the standard-of-care sorafenib in patients with advanced liver cancer.
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