A New Factor in Pancreatic Cancer?

Around 60,000 people in the United States will be diagnosed with pancreatic cancer each year. Unfortunately, about 75% of the newly diagnosed will live less than 1 year, leading to around 45,000 deaths per year. Overall, the 5-year survival rate for pancreatic cancer is only 9%. A big reason for this low survival rate is the lack of any early diagnostic or screening tests. Instead, diagnosis usually follows development of symptoms, such as abdominal pain or jaundice. However, pancreatic cancer symptoms are relatively silent until the disease is quite progressed, so most individuals have advanced disease before they are ever diagnosed. Advanced pancreatic cancer, especially with spread into local or distant tissues, is not effectively treated with current surgical and chemotherapeutic approaches.

A paper published last week in the journal Nature offers an intriguing new insight into pancreatic cancer and potentially provides novel targets for diagnostics and therapeutics. Drs. Saxena and Miller  of New York University, along with many colleagues, provide evidence for the role of a fungus in developing pancreatic cancer. Starting with a mouse model, these researchers showed that a fluorescently labeled test fungus did in fact pass from the stomach to the pancreas, consistent with this being the route of colonization of the pancreas. They then compared the actual fungi in pancreatic tissue from normal mice and from mice predisposed to develop pancreatic tumors (called KC mice). Tumors from the KC mice were highly enriched for fungi of the genus Malassezia. To examine the significance of fungal colonization, the KC mice were treated with antifungal agents (amphotericin B or fluconazole) to kill off endogenous fungi. Amazingly, both antifungal agents protected KC mice from development of pancreatic tumors. When these antifungal treated KC mice were repopulated with Malassezia pancreatic tumors developed. Repopulation of KC mice with other types of fungi (Candida, Saccharomyces, or Aspergillus) did not result in tumor formation, suggesting a critical role for Malassezia. The authors also found that Malassezia is enriched in human pancreatic tumors, though no drug testing was done in humans.

While many, many questions remain about a connection, if any, between Malassezia and human pancreatic cancer, this study opens new avenues for testing and treatment. Even if only a fraction of human pancreatic cancer has a fungal component, adding antifungal drugs to the current cancer treatments might greatly improve survival for some patients. Likewise, it may be possible to develop tests for Malassezia that could indicate patients at risk who could be treated with antifungal agents to forestall cancer development. It will be exciting to see where this study leads in the next few years.

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