Fox Chase Cancer Center Researchers Find Fungi May Impact Response to Treatment in Bladder Cancer

Laura Bukavina, MD, MPH
Laura Bukavina, MD, MPH, a Urologic Oncology Fellow at Fox Chase and first author on the paper.

PHILADELPHIA (December 22, 2022)—Research has shown that human immune function is highly correlated with the microorganisms living in the gastrointestinal tract. These microorganisms, known as the microbiome, can consequently impact whether a patient develops cancer and how they respond to treatment.

However, most research into the relationship between the microbiome and cancer has focused specifically on bacteria, the most prevalent microorganism in the gut. A recent study by Fox Chase Cancer Center researchers is the first to characterize the fungal component of the microbiome—known as the mycobiome—in patients with bladder cancer.

“We wanted to see what exactly is going on in terms of the mycobiome within the gut because that’s an unexplored area. We think the mycobiome is incredibly important due to its ability to modulate the immune response as well as small bioactive molecules,” said Laura Bukavina, MD, MPH, a Urologic Oncology Fellow at Fox Chase and first author on the paper.

The researchers not only were able to pinpoint specific differences among bladder cancer and healthy patients’ fungi in their gut, but they were also able to analyze how the presence of some of these fungi potentially affected response to chemotherapy. Although the research is in its infancy, they hope to pursue the mechanisms and meanings behind these differences in future research.

“The first step is to see what’s different between patients with cancer and normal patients, which is what we’ve done,” said Bukavina. “The second step will be to see if those differences are reproducible across multiple patients. Lastly, we need to figure out what potentially might be happening and how it can be leveraged to benefit the outcome of therapy.”

Bukavina’s coauthors included Robert Uzzo, MD, MBA, FACS, president and CEO of Fox Chase; Alexander Kutikov, MD, FACS, chair of the Department of Urology; and Phillip Abbosh, MD, PhD, an assistant professor in the Nuclear Dynamics and Cancer research program.

The researchers took stool samples from 29 bladder cancer patients and an equivalent number of healthy controls matched for age, body mass, and gender. When compared, the samples from the bladder cancer patients showed an overexpression of two fungi, Tremellales and Hypocreales.

Prior research has shown these microorganisms to be associated with more aggressive colon and pancreatic cancers. The researchers also found a reduction in Saccharomycetales, which made up only 50% of the mycobiomes in bladder cancer patients, compared to 95% in healthy patients.

Next, the researchers divided the bladder cancer group in two based on the presence or absence of remaining cancer in their bladder at the time of surgery to remove the bladder.

Saccharomycetales, which was already reduced in bladder cancer patients compared to healthy controls, was even more reduced for patients who experienced a complete response to treatment compared to those who did not. In patients who experienced a complete response, Hypocreales made up 27% of their mycobiome, compared to only 0.12% in patients with residual cancer.

“There’s likely a separation between the two groups,” said Bukavina. “People who respond to treatment have a cluster of fungi that are interacting not only with each other but also with the patient. We also know there’s a separate group of patients who don’t respond to chemo, and those patients host a different fungal community structure. However, the reason for those different community structures is unclear.”

The paper, “Human Gut Mycobiome and Fungal Community Interaction: The Unknown Musketeer in the Chemotherapy Response Status in Bladder Cancer,” was published in European Urology Open Science.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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