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Fungal involvement in tumors can lead to worse cancer outcomes
The presence of some fungal species in tumors predicts; and can even help with driving; to worse cancer outcomes, according to a study by researchers at Weill Cornell Medicine and Duke University. The study, appearing September 29 in Cell, provides a scientific framework for developing assays that describe specific fungal species in tumors that are relevant to predicting cancer progression and therapy. The results also suggest the possibility of supplementing traditional cancer treatments with antifungal treatments in some cases. “These results open up many exciting research directions, from the development of diagnostics and treatments to...
Fungal involvement in tumors can lead to worse cancer outcomes
The presence of some fungal species in tumors predicts; and can even help with driving; to worse cancer outcomes, according to a study by researchers at Weill Cornell Medicine and Duke University.
The study, appearing September 29 in Cell, provides a scientific framework for developing assays that describe specific fungal species in tumors that are relevant to predicting cancer progression and therapy. The results also suggest the possibility of supplementing traditional cancer treatments with antifungal treatments in some cases.
“These results open many exciting research directions, from the development of diagnostics and treatments to studies of the detailed biological mechanisms of fungal-cancer relationships,” said senior author Dr. Iliyan Iliev, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.
The first author of the study was Anders Dohlman, a doctoral student in biomedical engineering at Duke University.
The idea that viruses and bacteria can trigger or accelerate the development of cancer is now widespread. However, little is known about the cancer-related role of fungi, which, like bacteria and viruses, colonize the intestines, lungs, skin and other barrier tissues, interact with the immune system and sometimes cause disease.
In the new study, researchers cataloged fungal species and their associations with various cancers by analyzing the Cancer Genome Atlas, the largest well-annotated genomic database of human tumors.
The analysis revealed that the DNA of certain types of fungi is relatively abundant in some types of tumors. For gastrointestinal tumors, these species include Candida tropicalis and Candida albicans, which cause thrush and yeast infections; in lung tumors, species of the fungal genus Blastomyces; and in breast tumors, species of the fungus Malassezia.
The researchers developed sophisticated computational methods to exclude fungal DNA that likely came from laboratory contamination and, in particular, were able to confirm the presence of live Candida species in colorectal tumor samples.
Their analysis linked higher Candida levels in gastrointestinal tumors to tumor gene activity, which promotes inflammation and reduced cell-to-cell adhesion; Features associated with the spread of late-stage cancer to distant organs, known as metastasis. Higher levels of Candida in such tumors were also directly linked to a higher rate of metastasis.
According to the researchers, the results suggest that high concentrations of certain fungi in tumor biopsies could one day be used as biomarkers indicating, for example, a higher risk of metastasis - which in turn could lead to the choice of a more effective treatment.
Curiously, the researchers often discovered DNA from the same Candida species in both gastrointestinal tumor samples and in matched blood samples from the same patients.
These data are exciting because they lay the foundation for simple, cost-effective Candida DNA testing that can more accurately delineate the prognosis for gastrointestinal cancers, and complement standard DNA biopsies of tumors to enable early detection of these cancers before other signs are present.”
Dr. Steven Lipkin, co-author, Gladys and Roland Harriman Professor of Medicine and vice chair for research in the Sanford and Joan Weill Department of Medicine at Weill Cornell Medicine
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Dr. Lipkin is also director of the Cancer Genetics and Epigenetics Program at the Sandra and Edward Meyer Cancer Center and a clinical geneticist at NewYork-Presbyterian/Weill Cornell Medical Center.
It is conceivable that tumor-associated fungi could also be targets for antifungal therapies to improve overall treatment outcomes. However, this prospect hinges on an unresolved question: Do tumor-resident fungi help drive malignancy, perhaps by stoking inflammation, as some bacteria are known to do? Or are fungi associated with some tumors simply because the tumors, as they become more advanced, provide an increasingly permissive environment for fungal growth?
The researchers plan to pursue this and other lines of research in further studies, said Dr. Iliev.
"It is plausible that some of these fungi promote tumor progression and metastasis, but even if this is not the case, they could be very valuable as prognostic indicators," he said.
Source:
Reference:
Dohlman, AB, et al. (2022) A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors. Cell. doi.org/10.1016/j.cell.2022.09.015.
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