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Ascorbic acid + nab-paclitaxel + cisplatin + gemcitabine (AA NABPLAGEM) is an investigational combination chemotherapy regimen being evaluated by the Medical College of Wisconsin for the treatment of untreated metastatic pancreatic cancer. This regimen integrates high-dose intravenous ascorbic acid (Vitamin C) with a cytotoxic triplet backbone consisting of nanoparticle albumin-bound (nab)-paclitaxel, cisplatin, and gemcitabine. High-dose ascorbic acid acts as a pro-oxidant, generating hydrogen peroxide in the extracellular space that selectively induces oxidative stress and DNA damage in cancer cells while sparing normal tissue. Nab-paclitaxel is a microtubule-stabilizing agent that inhibits mitosis; gemcitabine is a nucleoside analog that inhibits DNA synthesis via ribonucleotide reductase inhibition; and cisplatin is a platinum-based alkylating agent that forms DNA cross-links. This multi-targeted approach aims to enhance the efficacy of standard-of-care chemotherapy in pancreatic ductal adenocarcinoma by leveraging synergistic mechanisms of DNA damage and metabolic stress.
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