A widely used class of drugs, many of which are available over the counter, may increase cancer cells’ sensitivity to radiation therapy, boosting the treatment’s efficacy while minimizing any additional toxicities, researchers reported in Oncotarget.
The researchers evaluated the radiosensitizing effect of proton pump inhibitors, specifically esomeprazole, in standard and radioresistant human head and neck squamous cell carcinoma cells in vitro and in mouse models. In both studies, they found that esomeprazole inhibited tumor growth and dose-dependently enhanced the effect of ionizing radiation in wildtype and p53-variant radioresistant cancer cells. Mice treated with espmeprazole and radiation had smaller tumors and fewer proliferating tumor cells, and the combination treatment significantly impaired tumor cells’ ability to self-repair following radiation-induced DNA damage.
They also found that esomeprazole regulates critical cell cycle proteins such as p21, p300, cyclin C, and ULK1. It upregulates p21 protein and inhibits cyclin-dependent kinases type 1 (CDK1) and type 2 (CDK2), thereby arresting cancer cells in the G1 cycle phase.
“Our studies indicate that esomeprazole sensitizes cancer cells to ionizing radiation and is associated with upregulation of p21 to arrest cells in the G1 phase of the cell cycle,” the researchers concluded. “Our findings have significant therapeutic implications for the repurposing of esomeprazole as a radiosensitizer in head and neck squamous cell carcinoma and other solid tumors.”