Fungi could be the key to major cancer research breakthroughs

Fungi could be the key to major cancer research breakthroughs

Two years ago, medical researchers taking a close look at cancer cells announced they had found a strange and surprising neighbor: fungi. But these fungi didn’t just live near tumors—they offered clues about how deadly the cancer might be. Candida yeasts associated with colon cancer were predictive of metastatic growth, while with gastrointestinal cancer, they correlated with poor survival rates.

It’s still too early to know if the fungi fuel the disease or if the disease is somehow incubating the fungi. But at the very least, these discoveries hint that there may be a new way to diagnose people earlier and better understand their prognosis.

“Initially, we were astounded,” says Iliyan Iliev, an immunologist at Weill Cornell Medicine in New York and one of the researchers who made the fungi-cancer connection. In addition to Candida, his team found several other fungal species that were associated with the disease, such as Blastomyces in lung cancer and Malassezia, a variety of yeast, tied to breast cancer.

(Here’s the guidance on lung cancer and breast cancer screenings.)

Viewed with a scanning electron microscope in this color-enhanced photo, Candida albicans is found in the human gut, or more  specifically the mycobiome. At high levels, it may  be linked to conditions like irritable bowel syndrome.

Photograph by Martin Oeggerli, Mycology, and Pathology, University Hospital Basel and Swiss Nanoscience Institute, Basel

Part of that surprise, for many, might be because of another link between fungi and our health. Medicinal mushrooms are sold throughout the world in various forms, from tinctures and capsules to powders and teas. They sustain a $30 billion business that’s expected to double by 2032, in part because of their cancer-fighting association.

Even so, researchers are still at an early stage of understanding the true benefits of medicinal mushrooms. In 2022, scientists in India and Belgium published a comprehensive survey of peer-reviewed literature on the topic. While at least 32 species showed promise, according to the report, only around a dozen had been clinically tested for their potentially therapeutic properties.

“Mushrooms produce a wide range of chemicals not readily found in other organisms,” says Walter Luyten, a professor emeritus at the Belgian university KU Leuven who contributed to the report. Some of these naturally derived compounds interact with the immune system to, as the report notes, “exhibit potent antitumor activity,” meaning they might slow the growth of certain cancers or even keep them from forming. Species such as reishi (Ganoderma lucidum) and maitake (Grifola frondosa), to name just two, have shown promise in clinical studies.

(Cancer vaccines are showing promise. Here’s how they work.)

Magic mushrooms—but hold the mushroom. Medicinal chemist Alex Sherwood prepares to isolate psilocybin hydrate crystals at the Usona Institute, a U.S.-based medical research organization. These macroscopic needle-like crystals spring from psilocybin molecules as they begin to cool over 30 hours after having been dissolved in heated solvent.

Photograph by Michael Christopher Brown (Top) (Left) and Photograph by Michael Christopher Brown (Bottom) (Right)

Though mushrooms are vastly understudied, Luyten and his team called them “one of the best gifts of nature for new … pharmaceuticals,” if we can better understand them.

This is the paradox of medicinal fungi: It’s a mysterious realm that could help or hurt us. Understanding this difference, and how best to harness what we’re learning, hinges on exploring a broader frontier called the mycobiome.

Your body is certainly no stranger to good or bad fungi. The yeast in your stomach that helps regulate digestion? That’s a good thing. The fungal infection on your skin that causes athlete’s foot? Not so much. Among the trillions of tiny microbes that live on or inside each of us in a delicate balance, there are bacteria, viruses, and single-celled protozoans, all of which are part of what’s known as your microbiome. Fungi are also included in that universe, but in recent years researchers have assigned them a separate designation— the mycobiome—in recognition that these organisms work quite differently.

(Humans are not prepared for a pandemic caused by fungal infections.)

Siew Ng, director of the Microbiota I-Center at the Chinese University of Hong Kong, says our body’s fungal community is a “small but crucial component” of the gastrointestinal microbiome in particular. But while gut fungi such as Candida, Saccharomyces, and Cladosporium are all fundamental to our health, they have also been linked to diseases. Candida, for instance, can overpopulate and cause dysbiosis, a disorder associated with many health issues, including colorectal cancer. In other words, good fungi can become too successful and run amok, and turn into bad fungi.

In a lab at the Usona Institute, chemists working to create synthetic psilocybin, among other projects, leave behind detailed notes, chemical ideas, and mechanisms on a fume hood window.

Photograph by Michael Christopher Brown

For Deepak Saxena, a microbiologist at New York University, the life-altering question is simple: Why do some fungi inhabit tumors? Saxena’s research group was the first to identify fungi in pancreatic cancer, finding in 2019 that a Malassezia yeast can migrate from the small intestine to the pancreas and inhabit cancer cells. Saxena hypothesizes that the fungi’s presence in the pancreas might be because of either immunosuppression or some other kind of altered environment that tumors help create. In lab experiments with mice, Saxena has seen the use of antifungal treatments arrest tumor progression, although plenty of research has shown that what works in mice often isn’t directly transferable to humans.

For mushroom experts, it’s not as simple as using one thing to treat another either. Ng says that traditional varietals like reishi and turkey tail (Trametes versicolor) have immune-boosting properties that have been shown to enhance the efficacy of chemotherapy. Numerous studies also indicate that many mushroom species do, in fact, contain anticancer compounds, including biologically active carbohydrates and terpenes that stimulate the immune system. Still, there are questions about what dose is most effective and whether any of these would work as a stand-alone treatment.

(The fungus in ‘The Last of Us’ is a real medicine—and it’s very, very expensive.)

Biologists at Utrecht University attempt to create a new generation of tempeh, a traditional Indonesian food created by fermenting soybeans. Using yellow peas, the biologists inoculate the legumes with several varieties of Aspergillus oryzae, a fungus which is also used in sake production, and compare results. The aim is to produce a tastier, easily digestible version of tempeh that provides high-quality protein.

Photograph by Michael Christopher Brown (Top) (Left) and Photograph by Michael Christopher Brown (Bottom) (Right)

In the meantime, there are no mushroom-based cancer drugs or immunity boosters on the market today that have been approved by the U.S. Food and Drug Administration. That makes any mushroom-related remedy sold over the counter with health claims essentially “try at your own risk.”

For some people, however, that seemingly untapped potential has led them to seek another kind of guidance.

On an overcast day this past October near Port Angeles, Washington, Robert Rogers tromped through a shady, wooded area followed by a dozen intrepid foragers who had signed up for his specially guided tour as part of the annual Olympic Peninsula Fungi Festival. He pointed to a fan-shaped fungus the size of a half-dollar growing on a decayed nurse log. Its earthen-hued bands resembled the plumage of a game bird. This is what turkey tail looks like in the wild, he told the crowd.

(Want to try foraging food? Here’s how to do it safely.)

The granddaughter of a licensed traditional herbal doctor, Ophelia Chong, pictured here with a batch of functional mushrooms, began cultivating fungi in Los Angeles nine years ago for personal medicinal and culinary use.

Photograph by Michael Christopher Brown

Rogers isn’t a doctor. He’s a self-described clinical herbalist and the author of The Fungal Pharmacy, a field guide to identifying mushrooms and lichens with purported health benefits. And he’s one of many ad hoc enthusiasts who have compiled research about incorporating fungi into everyday health routines, often as a preventive measure. Most commonly consumed mushrooms—even the ubiquitous grocery store button—have phytonutrients beneficial to our health. When it comes to cancer, however, medicinal fungi such as turkey tail are not exactly assassins. “They don’t kill cancer cells on sight,” he explains. “They encourage the immune system to do the job.”

Chong injects live mushroom tissue into a liquid culture of water mixed with honey, dextrose, or malt extract. (Sugar feeds the developing fungi.) After several weeks on a magnetic stir plate, the resulting mix is moved to a bag of grain and then soil, where it will eventually produce mushrooms for personal medicinal and culinary use.

Photograph by Michael Christopher Brown

More specifically, Ng says, turkey tail has been shown to increase the production of cytokines, which aid the body’s cellular response to fighting a foreign pathogen or tumor. Used traditionally for centuries, a chemical from the mushroom has been the focus of more than four dozen clinical trials to date.

(Turkey tail. Chaga. Lion’s mane. Do these mushroom supplements really help you?)

As for the connection between fungi and cancer cells, Iliev concedes that he initially considered it to be “biologically improbable,” but he’s since shifted toward “cautious optimism” about unraveling more mysteries of the mycobiome. In another recent study, researchers at NYU, including Saxena, found that there are 20 distinct types of fungi that may someday be useful in distinguishing between people with cancer and those without, pushing forward the idea that early testing of fungi might pave the way for better diagnoses and treatment.

Compare the potential advances of medicinal fungi to the advent of penicillin. One of the great fungi-based infection fighters of the modern age, it was discovered accidentally nearly a century ago, after a physician let mold grow in a petri dish of Staphylococcus bacteria. Who knows what other connections we might find now that we’ve started looking?

(A psychedelic surprise may be thriving in your local garden.)

This story appears in the April 2024 issue of National Geographic magazine.

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