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High-dose intravenous ascorbic acid (vitamin C) is an investigational therapy being developed by Sun Yat-sen University Cancer Center for the treatment of advanced or metastatic gastric cancer. While typically known as an antioxidant, at high pharmacological doses achieved through intravenous administration, ascorbic acid acts as a pro-oxidant, generating reactive oxygen species (ROS) and hydrogen peroxide within the tumor microenvironment. This oxidative stress leads to the depletion of intracellular glutathione and induces DNA damage, particularly in cancer cells with high GLUT1 expression. In clinical development, it is being evaluated as a first-line therapy in combination with chemotherapy regimens such as mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) or XELOX (oxaliplatin and capecitabine) to leverage synergistic anti-tumor effects, particularly with genotoxic agents like oxaliplatin.
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