Fungi promote tumor growth in pancreatic cancer patients

Research is on the rise to understand how the bacteria in our body affect tumor progression in cancer. But what about fungi, the other single-cell organisms that inhabit us?  What role do fungi play in tumor progression? When you think of fungal infections, you probably think of jock itch, yeast infection, ringworm, or athlete’s foot. Cancer isn’t what comes to mind. However, a new field in research looks at how fungi in our body affect tumor progression and cancer prognosis in patients. In the most surprising role to date, fungi are involved in one of the deadliest cancers—pancreatic cancer.

“A new field in research looks at how fungi in our body affect tumor progression and cancer prognosis in patients. In the most surprising role to date, fungi are involved in one of the deadliest cancers—pancreatic cancer."

-- Lily Neff

 Pancreatic cancer is the third leading cause of cancer-related death in the United States and has a five-year survival rate of approximately 9%. It is so deadly in part because it has no symptoms in its early stages. Symptoms that do appear in the later stages of tumor progression, such as appetite loss, weight loss, and yellowing of the skin, can be mistaken easily for symptoms of other diseases, leading to misdiagnosis. Furthermore, few treatment options are currently available for pancreatic cancer.  

 Researchers at the New York University School of Medicine reported in the October 10, 2019 issue of Nature that patients with pancreatic ductal adenocarcinoma (PDA), the most common form of pancreatic cancer, have a higher abundance of fungi in their pancreas than healthy individuals. They also showed that the gut and pancreas in PDA patients have distinct fungal compositions. By far the most abundant fungus in the pancreas but not the gut was Malassezi. This was a surprising finding, as Malassezi is mostly known for causing skin-related conditions, such as dandruff, eczema and dermatitis.

 Now we know that fungi are located within the pancreas, but which are responsible for increasing tumor size? To answer this question, the researchers set out to determine if multiple types of fungi were responsible for increasing the tumor size or if it was specifically Malassezi that did so. When the researchers injected mice with one of four different fungi that normally reside within our body, they found that only Malassezi accelerated PDA tumor growth.

Can antifungal drugs be used to help with tumor progression? To answer that question, the researchers tested the effects of antifungals used alone or in combination with chemotherapeutics. They showed that fluconazole, an antifungal, was not effective at reducing tumor size by a significant amount. However, when amphotericin B, an antifungal, and gemcitabine, a chemotherapy agent, were given together, they significantly reduced the tumor size within the pancreas. When the mice were given only one drug, either amphotericin B or gemcitabine, the tumor size was reduced but not as significantly as when the two drugs were given together.

Why is this research important? The data these researchers collected showed that Malassezi fungi relocate to the pancreas and increase PDA tumor growth. The data point to a potential new approach to treating PDA: combined use of antifungal treatment and chemotherapy. If proven successful at slowing disease progression or increasing survival in a future clinical trial, it could offer PDA patients a much-needed new treatment option.