Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer

Abstract

Pancreatic cancer accounts for nearly one fourth of all new cancers worldwide. Little progress in the development of novel or adjuvant therapies has been made over the past few decades and new approaches to the treatment of pancreatic cancer are desperately needed. Pharmacologic ascorbate (P-AscH−, high-dose, intravenous vitamin C) is being investigated in clinical trials as an adjunct to standard-of-care chemoradiation treatments. In vitro, P-AscH− has been shown to sensitize cancer cells to ionizing radiation in a manner that is dependent on the generation of H2O2 while simultaneously protecting normal tissue from radiation damage. There is renewed interest in Auranofin (Au), an FDA-approved medication utilized in the treatment of rheumatoid arthritis, as an anti-cancer agent. Au inhibits the thioredoxin antioxidant system, thus increasing the overall peroxide burden on cancer cells. In support of current literature demonstrating Au’s effectiveness in breast, colon, lung, and ovarian cancer, we offer additional data that demonstrate the effectiveness of Au alone and in combination with P-AscH− and ionizing radiation in pancreatic cancer treatment. Combining P-AscH− and Au in the treatment of pancreatic cancer may confer multiple mechanisms to increase H2O2-dependent toxicity amongst cancer cells and provide a promising translatable avenue by which to enhance radiation effectiveness and improve patient outcomes.

Keywords

• pharmacologic ascorbate
• vitamin C
• pancreatic cancer
• Auranofin
• thioredoxin
• thioredoxin reductase