External validation: Aykut et al 2019
In 2012, the discovery that PSP94 was a fungicidal protein firmly pointed to a fungal cause for prostate cancer (Stott-Miller 2013, Sutcliffe 2014). Since then, the most incriminating evidence against Malassezia has stemmed from psoriasis, Crohn's disease and ankylosing spondylitis—not from prostate cancer.
Apart from Stott-Miller 2013 and Sutcliffe 2014, evidence supporting a fungal cause in prostate cancer was limited to the efficacy of antifungal drugs. The absence of fungi other than Malassezia in the prostate suggested they were the culprits. However, this evidence fell short of convicting Malassezia for prostate cancer—that is until 2018, when we managed to demonstrate that Malassezia were main the cause of psoriasis, Crohn's disease and ankylosing spondylitis (Laurence 2018).
On October 2nd 2019, researchers from NYU published an article in Nature convincingly pinning pancreatic cancer on Malassezia (Aykut 2019). This article marks a major turning point in understanding the cause of pancreatic cancer, and provides a new therapeutic target: killing Malassezia with antifungal drugs. This treatment was effective in mouse models of pancreatic cancer (Aykut 2019). It has not yet been tested in humans.
Since the beginning of this project, I’ve suspected that fungi play a role in cancers whose onset occurs later in life—simply because of PSP94's distribution in the body:
“The final major insight is related to PSP94‘s distribution in the body: its gene is expressed in all late onset cancer sites [...] This is unlikely to be a coincidence. PSP94 probably plays a role in preventing most late onset cancers, as it does in the prostate.” -PSP94, what is it good for? (October 2012)
PSP94 is produced by human cells in the pancreas which are susceptible of becoming cancerous; it is also produced in the prostate, breast, colon, lung, cervix, uterus, liver, stomach, kidney and esophagus (Weiber 1990; Ohkubo 1995; Sheth 1993; Baijal-Gupta 2000). These are the organs at highest risk of developing cancer in old age. So far, Malassezia have been found in the breast (Boix-Amoros 2017), pancreas (Aykut 2019), mouth (Dupuy 2014; Abusleme 2018), lung (Nguyen 2015), prostate (Laurence 2016), colon (Nash 2017; Limon 2019) and cervix (Godoy-Vitorino 2018).
Similarly to pancreatic cancer:
Malassezia have been associated with cervical cancer risk (Godoy-Vitorino 2018).
This raises the possibility that:
PSP94 is produced by the body to protect human cells from Malassezia.
Malassezia are involved in all cancers which develop where PSP94 is found.
Antifungal drugs might prevent or cure these cancers, by giving PSP94 a helping hand.
Verifying the presence of Malassezia in all PSP94-positive sites in the body is urgent. Wherever Malassezia are found, it is imperative to test if antifungal drugs can prevent or cure cancers of colonized organs.