Two recently published studies in the scientific journal Cell relaunch the hitherto little researched possible relationship between fungal microorganisms in the body and the advancement of metastases.
For several years now, the associations between certain bacterial or viral infections and tumours have become increasingly evident. In some cases a direct link between infection and the development of neoplasia has been demonstrated. Vaccines, when available, have proved able to virtually eliminate the incidence of the relevant tumour; for example, the papillomavirus infection (certain strains of this virus are considered to be the main cause of cervical cancer).
The other large family that co-habit the human body – fungi - have always received less attention, partly because relatively little is known about them. Now, however, two studies, published in the same issue of the scientific journal Cell, are relaunching the idea of these micro-organisms, which are regular guests on our bodies (the best known is vaginal candida, but there are many others) often without causing problems.
In the first study, researchers from the Weizmann Institute of Science in Rehovot, Israel, identified the presence of fungal DNA in over 17,000 samples of 35 different types of tumours, and confirmed it was present in all. They noticed some distinctive features. For example, the fungus called malassezia globosa, already suspected of being linked to pancreatic cancer, is also found in large quantities in the most aggressive breast cancers, which have low survival rates.
Nothing more specific can be said for the moment, because establishing an association does not mean proving a cause-and-effect relationship, but clearly what has emerged in several cases deserves further study.
The Israeli researchers then looked further, checking for the co-presence of bacteria. They discovered that when a large quantity of fungi are present they tend to always be accompanied by the same bacterial species. This is also an unusual situation, because normally, where there is no tumour, families compete with each other, and one prevails.
In the second study, however, researchers at Cornell University in New York analysed sample data from the largest and most comprehensive US archive on cancer genes, the Cancer Genome Atlas, focusing on gastrointestinal tract, lung and breast cancers.
They discovered that the former tend to contain several species of candida, like the well-known albicans, as well as tropicalis, while those of the lung are more likely to harbour blastomyces, and those of the breast malassezia, thus indirectly confirming the Israeli colleagues' findings on the latter.
Fungal infections and tumours: data to be evaluated with caution
It must be said that these studies are as pioneering as they are controversial: fungi are very rare within tumour masses, to the extent that the ratio is about one fungus to every 10,000 cells.
Also, as mentioned above, they are everywhere in the human body, and we cannot therefore exclude the possibility that the samples in both studies - taken without thinking about the possibility of fungal research and the risk of contamination - also contained spurious material, which may have distorted results. Finally, it is possible that fungi are only present in the tumour because the tumour itself has caused the immune system to weaken.
While bearing these special features and evaluation risks in mind, the researchers in both studies believe that these results are interesting, and therefore intend to continue, mainly to understand the scenario as a whole. It is indeed possible that a fungal infection, which causes inflammation and affects the compactness of cells, helps metastases to form (fungal infections have already been associated with metastases in the past, in other studies). However, it is also possible that as the tumour grows, it creates a microenvironment that is particularly favourable for fungi to take hold. The priority is therefore, is to try and establish the true sequence of events.
Antifungal/anti-cancer drugs: developments in treatments
As far as possible applications are concerned, it is clear that if fungi have a role in metastasis or even just keeping cancerous masses alive, an anti-cancer use of already approved antifungal drugs could immediately be explored, although there are very few of them and almost all the fungi circulating in the world today appear resistant to those molecules.
However, new drugs could be developed. The presence and quantity of fungi in a biopsy sample could also be used as an indicator of malignancy, or of response to treatment.