Heartburn medication potential key to fighting cancer and immune disorder in canines

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Texas A&M School of Veterinary Medicine and Biomedical Sciences (VMBS) researchers recently discovered that proton pump inhibitors (PPIs), commonly used to treat acid reflux and heartburn in people and animals, could potentially be effective at fighting cancer and other immune disorders in dogs.¹ These findings are also building on similar ongoing research in human medicine.

“While we can’t use PPIs alone to treat cancer, we’re hopeful that we may be able to improve the effectiveness of chemotherapies by combining them with PPIs sometime in veterinary medicine in the future,” explained Emily Gould, DVM, MS, DACVIM (SAIM), PhD, an assistant professor in the Department of Small Animal Clinical Sciences at VMBS, in an organizational release.¹ “Using them at certain stages of cancer treatment may improve treatment success.”

According to the release, proton pumps are considered “channels" that regulate how different molecules are distributed throughout the bodily systems.¹ Although they have been designed to govern stomach acid production, recent research suggests these medications could also affect other types of pumps within the body, including immune cells or cancer.

A study that was recently published in the journal Veterinary Immunology and Immunopathology investigated which cellular systems affect PPI, with hopes the findings will give both human and animal medicine experts a more holistic understanding of PPI effects.² The researchers found that their work demonstrated treatment of neoplastic in vitro MCs from multiple species with esomeprazole, more so than famotidine, alters cell structure, induces significant cytotoxicity, and could even alter murine mast cells.

“Cancer cells have their own microenvironment; acidic conditions help drive inflammation and metastasis — the growth of additional cancer tumors,” said Gould.¹ “They have their own proton pumps called vacuolar ATPases, or V-ATPases, that, among a lot of other factors, help create those acidic conditions. Our research suggests that PPIs might inhibit these pumps in addition to the ones in gastrointestinal cells.”

V-ATPases are one mechanism some tumors will use to assist cancer cells in resisting chemotherapies, in addition to a pro-tumor microenvironment. Gould explained combining PPIs with chemotherapy could make the treatment more successful because it could potentially turn off or stop the ability of cancer cells to resist chemotherapy.

However, using PPIs to treat cancer has its challenges. For example, PPIs appear to inhibit proton pumps inside immune cells, including mast cells. The researchers at Texas A&M believe that timing would be a crucial element in using PPIs in cancer treatment.¹

“Mast cells, and other innate immune cells, also have V-ATPase pumps, and they play a role in regulating when the white blood cells release critical molecules that help fight off disease and inflammation. They keep many of these molecules in what are called granules — they’re basically little toolboxes inside the white blood cells. We think that PPIs can inhibit some white blood cells from using their toolboxes effectively,” said Gould.

“Other types of white blood cells don’t have those toolboxes, but that doesn’t mean PPIs aren’t affecting them, likely via several different mechanisms. That’s something we want to examine in future studies,” she continued.¹

PPIs have been used to help human and animal patients manage gastrointestinal problems like acid reflux, but there is still a lot researchers do not know about this family of drugs. At this time, Gould is running clinical trials for dogs with mast cell tumors on their skin to determine if PPIs have a positive effect in reducing the adverse effects of their cancer. Anyone interested in learning more about the trial can visit the Texas A&M’s Department of Small Animal Clinical Sciences.

“PPIs can do more than just manage pH levels in the stomach. For example, they also have anti-inflammatory and antioxidant properties. This project really began because we wanted to better understand the drugs that we prescribe very commonly in veterinary medicine. Then we read about the studies being done in human medicine with PPIs and cancer and decided we need to see how they might translate to helping dogs,” Gould concluded.

References

1. Price C. Common heartburn medications may help fight cancer and other immune disorders in dogs, Texas A&M researchers find. Texas A&M Today. Published May 23, 2024. Accessed May 24, 2024. https://today.tamu.edu/2024/05/23/heartburn-medications-may-help-fight-cancer/
2. Gould EN, Szule JA, Wilson-Robles H, Steiner JM, Lennon EM, Tolbert MK. Esomeprazole induces structural changes and apoptosis and alters function of in vitro canine neoplastic mast cells. Vet Immunol Immunopathol. 2023;256:110539. doi:10.1016/j.vetimm.2022.110539