Thread by @SPeribsen

My suspicion is the root of cancer will prove to be HGT (horizontal gene transfer) from fungal pathogens via extracellular vesicles. There are many moving parts to this theory that require testing of course, so I'm going to outlay what I'm seeing in this thread.

The research I have been engaged in has focused on the underpinnings of apparent disease progression, and in many cases, initiation related to invasive fungal diseases. There is a particular disease set known as APECED that is a key to this. See attached ncbi.nlm.nih.gov/pmc/articles/P…

APECED presents various symptoms as a result of the genetic dysfunctions that it relates to. These are primarily immune response issues and autoimmune complications. The study below reflects the impacts very clearly as compared to standard populations. ncbi.nlm.nih.gov/pmc/articles/P…

What stands out are the increased occurrences of malignancy, among other chronic disease patterns. A piece of the underlying theory is these increases tie to the immune issues whereby this range of fungi (yeasts) bypass the immune system and initiate inflammatory responses.

One concern is the relative rarity of APECED outside populations highlighted in the first linked article. For this it's important to note that there are many "fractional" presentations of related errors. This impacts certain interleukins that prevent fungal access to our systems.

Examples of these fractional presentations would be chronic mucocutaneous candidiasis/familial candidiasis. The results are roughly the same, involving interleukin issues around il-17/22. The link below explains this. ncbi.nlm.nih.gov/pmc/articles/P…

With this information at hand I started chasing underlying connections between cancer and invasive fungal disease. Early in my reading I came across a set of images that gave some direction. The stages of progression for each range of disease matched very closely.

Fungi, cancer, autoimmune issues, and inflammation all showed links in the data quickly. What became difficult was a mechanism that would explain the mitochondrial changes that show in cancer progression. Cellular functions do match closely between tumors and fungal colonies.

The first target in the yeast range of microbes that presented a possibility was Candida Albicans. Candidalysin, a toxin produced only by Albicans had been identified in 2019. It is a cytolysin and triggers NLRP3 issues known in cancer research. ncbi.nlm.nih.gov/pmc/articles/P…

Other species cause various inflammatory responses: aspergillus, cryptococcus, malassezia, saccharomyces. See the images below for mechanisms related to Albicans invasion of epithelial cells. Although this shows the damage, still no direct DNA/RNA changes indicated.

This lead to a pause in the manuscript I had submitted most of to my editor @mheneise (without whose guidance and ear this theory would have stalled). There was active penetration of the cell and a lysing agent causing inflammation. NLRP3 activation wasn't enough for me.

Then a series of studies were released in late 2022. Both of which indicated involvement of fungal genetics in all cancer cells analyzed. This was no small sample size either. 17,500 across 35 cancer types. And most of the species indicated were Saccharomyces.

I'll link the related studies in a block here. They are worth reading through as they show that the genetics of yeasts were in every sample, but no clear indication as to why.


qps.com/2022/10/31/res…
cell.com/cell/fulltext/…
cell.com/cell/fulltext/…

This brings us to the theory I'm presenting for scrutiny as related to mitochondrial changes. The behavior of tumor cells alongside the fungal DNA/RNA in the samples from those studies requires some sort of exchange. Your cells don't initiate switching on their own.

A mechanism that is becoming well known among pathogens is horizontal or lateral gene transfer. Meaning that sections of DNA/RNA can be pushed to a different organism's cell - both nuclear and mitochondrial gene can be affected. labroots.com/trending/cell-…

So that information shows that for transfer of DNA/RNA from one cell to another, contact is not required. Transfer is initiated via Extracellular Vesicles (EVs). These are produced by pathogens and can insert genetic information to host cells. frontiersin.org/journals/oncol…

We now have a model coming to view that EVs could explain this change of cellular function in healthy mammalian cells at the mitochondria level. These functions change to such degree that these altered cells function to support fungal colony requirements.
frontiersin.org/articles/10.33…

Let's get more specific now. We need to see the occurrence of EVs clearly indicated in the pathogens I propose drive cancer initiation to a major degree. This study clearly shows the biogenesis of fungal EVs and cites other studies the last paragraph. ncbi.nlm.nih.gov/pmc/articles/P…

As mentioned previously, Saccharomyces species were the major players in the cancer analysis. Here we see that EVs are produced by these species, allowing for cell wall remodeling and antifungal avoidance. The question of HGT was also addressed above. nature.com/articles/s4200…

For Candida Albicans, this study shows related proteins in the EVs released in both yeast and hyphal forms. The hyphal EVs are quite complex genetically and impact immune response in the host. This would allow for HGT in the model presented. journals.asm.org/doi/full/10.11…

And last in line would be Cryptococcus Neoformans. Extracellular vesicles from Cryptococcus are very complex and outside cancer implication could be seen as serving similar functions to a virus. Nearly every component needed for infection is present. mdpi.com/2076-0817/9/9/…

These are the major points of my theory on cancer initiation by fungal extracellular vesicles. There are specific analyses required at this point, which I am sorting through details of with @mheneise and the Institute. I welcome questions and we need more eyes on it.

One note I will leave off with is that I have already submitted experiment methodology to Dr. Heneise and we are currently seeking advisement on placing the experiment. It is cell-line only and should rest this theory fully, allowing for others to follow the marks.

@JonMajerowski @anecdoted @Deepfryguy76 @OldVetSymposium @mheneise @_MacLir @A_Hawktopus @fringe_think @MissSpookyMoo @covertress