Do the fungi that hide inside cancers accelerate their growth?

The mushroom candidiasis – shown here growing under laboratory conditions – has been found in some tumor samples.Credit: Nicolas Armer/dpa/Alamy

For years, evidence has been accumulating that bacteria are linked to cancer, and sometimes even play a crucial role in its progression. Now, researchers have found a similar link with another type of microorganism: fungi.

According to two studies published in Cell September 291,2. “It’s fascinating to look at fungi in the context of cancer,” says Ami Bhatt, a microbiome scientist at Stanford University in California. But she warns that the studies only suggest there is an association between fungal species and certain cancers – they don’t show whether or not the fungi are directly responsible for cancer progression.

Indoor microbes

Like bacteria, fungal microorganisms form a crucial part of the human microbiome – a delicate balance of microbes living inside the body. To understand how this composition might be altered in people with cancer, Lian Narunsky Haziza, a cancer biologist at the Weizmann Institute of Science in Rehovot, Israel, and her colleagues cataloged the fungal populations in more than 17,000 samples of tissues and blood representing 35 types of cancer.1.

As expected, fungi, including several types of yeast, were present in all cancer types included in the study, but some species were linked to different outcomes, depending on the cancer. For example, the presence of Malassezia globosa, a fungus that was previously associated with pancreatic cancer, was linked to significantly reduced survival rates in breast cancer, the researchers found. By also characterizing the bacteria in the tumors, Narunsky Haziza and his colleagues discovered that most types of fungi had certain bacterial species with which they tended to coexist, meaning that the tumor could support both fungal growth and bacterial – unlike typical environments, in which fungi and bacteria compete for shared resources.

In another study2immunologist Iliyan Iliev of Weill Cornell Medicine in New York and his colleagues examined gastrointestinal, lung and breast tumors and found that they tended to contain candidiasis, Blastomyces and Malassezia mushrooms, respectively. Higher levels of candidiasis in gastrointestinal tumor cells were linked to greater gene activity that promotes inflammation, a higher rate of metastasis and lower survival rates, the researchers found.

Characterizing fungal cells in a tumor is like finding a needle in a haystack, says Deepak Saxena, a New York University microbiologist who has studied the fungus-cancer link. Depending on the sample, there’s usually only about one fungal cell for every 10,000 tumor cells, he says.

Additionally, many of the fungal species in question are widespread, making sample contamination a serious concern, Iliev says. This meant that researchers had to take great care to filter out any potential evidence of contamination or false matches for fungal DNA from their results. For example, Iliev and his colleagues found a DNA fragment misidentified as a Portobello mushroom (Agaricus bisporus), a common edible fungus, in tumor tissues throughout the body.

Both research teams obtained most of their tissue and blood samples from databases, so the samples were not collected in an effort to minimize fungal contamination, Bhatt says. Although the researchers have developed methods to filter out any potential contaminants from the sequencing data, she would like to see the results reproduced using samples taken in a sterile environment.

Fungal effects

While this research provides the clearest link to date between cancer and mushrooms, Saxena says more work is needed to understand whether mushrooms can contribute to cancer progression by causing inflammation, for example, or whether advanced tumors create a habitable environment that encourages fungal cells to take hold. .

To answer these questions, researchers will need to study one type of cancer at a time and use lab-grown cells and animal models to test whether fungi encourage healthy cells to become cancerous, says Charis Eng, a cancer geneticist at the Cleveland Clinic in Ohio. Once researchers better understand the role of fungi in cancer, they may be able to develop therapies or probiotics that control fungal populations, which could help stop cancer progression, Eng says.

It will also be important to piece together how bacteria, viruses and fungi interact and contribute to cancer, says Nadim Ajami, microbiome specialist at MD Anderson Cancer Center in Houston, Texas. “We know that these ecologies co-exist,” he says. “When we only think of bacteria or fungi, we tend to forget that they live in the same environment.”

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