Nicole Zhao ’20

Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide and occurs more frequently in developed countries (1). What makes pancreatic cancer even more alarming is that patients seldom exhibit symptoms until an advanced stage of the disease when little can be done for them (1). Therefore, techniques in early detection and risk assessment are crucial in the prognosis of a disease and which treatment options are available to patients. Previous research has found that bacterial dysbiosis is associated with the disease pancreatic ductal adenocarcinoma (PDA) (2). An adenocarcinoma is cancer that begins in the gland cells that line certain internal organs such as the ducts of the pancreas (3). Moreover, 95% of pancreatic cancers are PDA (4). However, the role of the fungal microbiome in pancreatic cancer has not yet been explored. In a 2019 study, researchers found that gastrointestinal fungi can migrate to the pancreas and cause PDA (5).

This novel study led by Dr. Miller at New York University found that cancer arising in the pancreatic duct was associated with a 3,000-fold increase in fungi seen in human and mouse models, compared to normal pancreatic tissue (5). This is surprising since the pancreatic duct, where secretive enzymes pass through into the small intestine, was previously thought to be sterile. Furthermore, it was found that the genus of fungi Malassezia spp., was found to be the most abundant in PDA (5). The genus of fungi Malassezia is typically found on the skin and is associated with dandruff, eczema and other skin diseases (6). 

To confirm whether the presence of the fungus was the cause of cancer, researchers administered an antifungal drug to the mouse models with PDA (5). This treatment effectively got rid of the fungi and kept pancreatic tumors from developing. However, when these treated mice were exposed to the fungi, the tumors started to grow again (5). This proved that the fungi Malassezia was driving the growth of tumors. It is important to note that this conclusion could be made because induction of different fungi had no effect on the growth of tumors (5).

Although the presence of fungi might not be the only explanation for the cause of pancreatic cancer, understanding the fungi microbiome is important to unraveling the complicated disease. This novel study and its findings suggest that the fungi Malassezia is associated with PDA and was found to promote pathogenesis upon its induction. Therefore, fungal microbiota may become a new target for therapeutic agents and an area of discovery for biomarkers that can detect the disease early. 

References:

1. P. Rawla, et al., Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncology 10(1): 10–27 (2019). doi: 10.14740/wjon1166. 
2. S. Pushalkar, et al., The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov. 8, 403–416 (2018). doi: 10.1158/2159-8290.CD-17-1134. 
3. NCI dictionary of cancer terms. National Cancer Institute. 
4. Types of pancreatic cancer, Pancreatic Cancer UK (2018). 
5. B. Aykut, et al., The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 574, 264–267 (2019). doi: 10.1038/s41586-019-1608-2. 
6. C. W. Saunders, et al., Malassezia fungi are specialized to live on skin and associated with dandruff, eczema, and other skin diseases. PLoS Pathog. 8(6) (2012). doi: 10.1371/journal.ppat.1002701
7. Image retrieved from: https://pixnio.com/science/microscopy-images/malassezia-lipophilis/malassezia-lipophilis