The Role of Fungus in Cancer
STORY AT-A-GLANCE
·
Research shows fungi can migrate from your gut to your pancreas,
where it can contribute to the development of pancreatic cancer. In mouse and
human models, pancreatic tumors contain 3,000 times more fungi than normal
pancreatic tissue
·
Pancreatic tumors had far greater amounts of a common fungal
genus called Malassezia. Using an antifungal drug was found to be protective,
slowing down the progression of the tumor
·
The fungi trapped in the pancreas appears to drive tumor growth
by activating MBL (mannose-binding lectin), a liver protein that triggers an
immune mechanism involved in fighting infections
·
Solid tumors excrete acid and the spread of cancer cells is
stimulated by acidic conditions in the surrounding tissues. Acid is a byproduct
of glucose metabolism, which ties in with research showing cancer feeds on and
is accelerated by a diet high in sugar
·
Previous research suggests baking soda can be helpful for
inhibiting cancer metastasis. It also appears to improve the effectiveness of
other cancer treatments
Oftentimes,
even the most unlikely-sounding theories can be scientifically validated if you
just wait long enough. That certainly rings true for recent headlines declaring
fungi and bacteria may be playing a role in the development of certain types of
cancer, combined with previous research showing baking soda may be a useful
remedy. In 2011,
ScienceBasedMedicine.org shamed Dr. Oz for allowing me on his show,1 and one of the
"reasons" given was that I had at one time published information about
a novel hypothesis — the idea that cancer could be caused by common
fungi and might be treatable with baking soda.
Two early proponents of this hypothesis were Tullio Simoncini2,3 and
Mark Sircus.4 As you might expect, they were unsuccessful in their attempts at
getting the conventional medical establishment to take the hypothesis seriously
and have been maligned and marginalized for promoting these ideas. So, mark my surprise when October 3, 2019, The
New York Times published an article5 titled, "In the
Pancreas, Common Fungi May Drive Cancer." The article reported the
findings of a study6,7 published in the October 2019 issue of
the prestigious Nature journal. According to this study:8
"Bacterial dysbiosis accompanies carcinogenesis in
malignancies such as colon and liver cancer, and has recently been implicated
in the pathogenesis of pancreatic ductal adenocarcinoma (PDA). However, the
mycobiome has not been clearly implicated in tumorigenesis. Here we show that fungi migrate from the gut
lumen to the pancreas, and that this is implicated in the pathogenesis of PDA.
PDA tumors in humans and mouse models of this cancer displayed an increase in
fungi of about 3,000-fold compared to normal pancreatic tissue."
Fungal Microbiome May Play a Role in Pancreatic Cancer
More
specifically, the mycobiome (the fungal microbiome) found in pancreatic tumors
was distinctly different from the mycobiome found in the gut and in normal
pancreases. According to the
researchers, PDA tumors had far greater amounts of a common fungal genus called
Malassezia. Killing off the mycobiome with an antifungal drug was found to be
protective, slowing down the progression of the tumor. As reported by Medical
News Today:9
"The team found that treating mice with a strong antifungal
drug called amphotericin B reduced tumor weight by 20–40%. The treatment also
reduced ductal dysplasia, an early stage in the development of pancreatic
cancer, by 20–30%. Antifungal treatment
also boosted the anticancer power of gemcitabine, a standard chemotherapy drug,
by 15–25% …"
On the
other hand, repopulating the tumor with Malassezia accelerated tumor growth,
except when Candida, Saccharomyces or Aspergillus genera were used. This
suggests Malassezia is the main culprit in this kind of cancer. When other
genera were included, tumor growth was much slower.
"We also discovered that ligation of mannose-binding lectin
(MBL), which binds to glycans of the fungal wall to activate the complement
cascade, was required for oncogenic progression, whereas deletion of MBL or C3
in the extratumoral compartment … were both protective against tumor
growth," the authors note,10 concluding that:
"Collectively, our work shows that pathogenic fungi promote
PDA by driving the complement cascade through the activation of MBL." In summary, the fungi trapped in the pancreas
appears to drive tumor growth by activating MBL (mannose-binding lectin), a
liver protein that triggers the complement cascade11 — an immune mechanism
involved in fighting infections. The
problem is that this mechanism can also promote the growth of cells after the
infection has been resolved.12,13 When MBL activation was inhibited, tumor growth
was also inhibited.14
Microenvironment Is an Important Consideration
As
reported by The New York Times,15 up until very recently, the pancreas was
thought to be a sterile organ, which made these findings all the more
surprising. The New York Times goes on to state:
"There is increasing scientific consensus that the factors in
a tumor's 'microenvironment' are just as important as the genetic factors
driving its growth. 'We have to move
from thinking about tumor cells alone to thinking of the whole neighborhood
that the tumor lives in,' said Dr. Brian Wolpin, a gastrointestinal cancer
researcher at the Dana-Farber Cancer Institute in Boston. The surrounding healthy tissue, immune
cells, collagen and other fibers holding the tumor, as well as the blood
vessels feeding it all help support or prevent the growth of the cancer. Microbes are one more factor to consider in
the alphabet soup of factors affecting cancer proliferation. The fungal
population in the pancreas may be a good biomarker for who's at risk for
developing cancer, as well as a potential target for future treatments. 'This is an enormous opportunity for
intervention and prevention, which is something we don't really have for
pancreatic cancer,' said Dr. Christine Iacobuzio-Donahue, a pancreatic cancer
researcher at Memorial Sloan Kettering in New York." That this research is being taken seriously is
evidenced by its widespread media coverage. As reported in an accompanying
article in Nature News and Views:16 "The mycobiome is a
historically under-recognized player in human health and disease, but its role
in both is essential. Harmless organisms called commensals, including fungi,
inhabit mucosal surfaces such as the linings of the gut, nose and mouth, and
can activate inflammatory processes as part of the immune system's response to
injury or infection … Moreover, it is
becoming apparent that there is a relationship between the gut mycobiome and
human cancers, including colorectal and esophageal cancer."
Baking Soda Inhibits Cancer Metastasis
While the
featured Nature study did not address the potential use of baking soda (sodium bicarbonate),
research17 published in the
journal Cancer Research in 2009 did. According to the abstract:18
"The external pH of solid tumors is acidic as a consequence
of increased metabolism of glucose and poor perfusion. Acid pH has been shown
to stimulate tumor cell invasion and metastasis in vitro and in cells before
tail vein injection in vivo. The
present study investigates whether inhibition of this tumor acidity will reduce
the incidence of in vivo metastases. Here, we show that oral NaHCO3 selectively
increased the pH of tumors and reduced the formation of spontaneous metastases
in mouse models of metastatic breast cancer.
This treatment regimen was shown to significantly increase the
extracellular pH, but not the intracellular pH, of tumors … NaHCO3 therapy also
reduced the rate of lymph node involvement, yet did not affect the levels of
circulating tumor cells, suggesting that reduced organ metastases were not due
to increased intravasation. In
contrast, NaHCO3 therapy significantly reduced the formation of hepatic
metastases following intrasplenic injection, suggesting that it did inhibit
extravasation and colonization." The authors point out that
the extracellular pH of malignant tumors typically ranges between 6.5 and 6.9,
whereas normal tissues have an alkaline pH typically ranging between 7.2 and
7.5. They also cite previous
studies showing solid tumors excrete acid and that the spread of cancer cells
is stimulated by acidic conditions in the surrounding tissues. The paper also
points out that "acid is a byproduct of glucose metabolism," which ties
in with research showing cancer feeds on and is accelerated by a diet high in
sugar.
In this
experiment, mice injected with cancer cells were given either plain drinking
water or water with 200 mmol/L bicarbonate. Calculations suggest the equivalent
dose in human terms would be 12.5 grams (0.4 ounces) of bicarbonate per day for
an individual weighing 154 pounds or 70 kilos. While the bicarbonate
therapy had no effect on the rate of growth of the primary tumors, it did
significantly reduce the number and size of metastatic tumors in the lungs,
intestines and diaphragms, which in turn resulted in improved survival.
According to the authors:19 "In the 30-day
experiment, pooled data showed that the bicarbonate-treated mice had a total of
147 metastatic lung lesions, whereas the control group had 326 lung lesions.
The average lesion diameters were 4.5 ± 0.12 and 5.2 ± 0.14 mm in the NaHCO3
and control groups, respectively."
Baking Soda Might Not Be as 'Quack' as You Thought
In 2012,
Mark "Marty" Pagel Ph.D., associate professor of biomedical
engineering at the University of Arizona, was given a $2 million grant to
investigate whether drinking baking soda water might help patients with breast
cancer.20,21 Interestingly, while the use of baking soda in
the treatment of cancer has been written off as the worst possible type of
quackery by skeptics and critics, the University of Arizona Cancer Center has actually
been studying its use for nearly two decades. As reported by Cancer Active in
2017:22 "… in 2003 (Raghunand)
they showed how drinking sodium bicarbonate resulted in the alkalization of the
area around cancer tumors resulting in a cessation of new metastases23 …
Further research has shown that sodium bicarbonate had an effect
on breast and prostate cancers but had mixed results with other cancers … 2009,
Robey et al showed that drinking sodium bicarbonate caused new metastases to
stop, whilst injection of Bicarbonate into tumors caused regression of the
cancer24 … Ed: At
CANCERactive we have a simple view that is identical to that of American cancer
researcher Ralph Moss. This is research every cancer patient should know about.
If drinking sodium bicarbonate can restrict cancer metastases then it should be
considered as a part of an Integrated Cancer Treatment Programme, especially if
it enhances the action of chemotherapy drugs." While Pagel's team has published a number of
studies since then, including one detailing the ways in which extracellular pH
can be assessed inside in vivo tumors,25,26 they've not yet
published anything discussing the use of baking soda as an adjunct to breast
cancer treatment.
Baking Soda Found to Improve Cancer Treatment
More recently, a study27 published in 2018
concluded the addition of baking soda can improve the effectiveness of
conventional cancer treatments. According to these findings, published in the
journal Cell, when tissues are acidic, cancer cells can go dormant, thereby
allowing them to hide from the treatment. Lead author Chi Dang told WhyY.org:28 "Many of the therapies
we have — chemotherapy, targeted therapy — work in cells that are actively
functioning and dividing. When you awaken cells from a resting state into an
active state, they become more vulnerable to cancer therapy." This study also found that when pH is low, it
disrupts your circadian clock. "Buffering against acidification or
inhibiting lactic acid production fully rescues circadian oscillation,"
the researchers found.29 Acidification also suppresses mechanistic target of
rapamycin complex 1 (mTORC1) signaling, and this too plays a role. According to
the authors: "Restoring mTORC1
signaling and the translation it governs rescues clock oscillation. Our
findings thus reveal a model in which acid produced during the cellular
metabolic response to hypoxia suppresses the circadian clock through diminished
translation of clock constituents."
WhyY.org expounds on the findings:30
"'What we've discovered in this study is that there's a very
rapid mechanism by which low pH, or acid itself, turns off a key toggle in the
cells that controls the cell's ability to make proteins,' Dang said. In other
words, it prevents cells from dividing. As
their processes slow down, the cells go into hibernation, making them invisible
to cancer treatments. Dang and his team wanted to see if they could reverse
that process, and they came up with a simple solution:
neutralizing the acid with baking soda.
They tested their theory by adding baking soda to the drinking
water of mice that had been grafted with tumors. 'What we found is that the
areas that were acidic, now are no longer acidic, and they become more active,'
Dang said. 'So this toggle comes back on,
so that cells that are at rest can now be reawakened.' That allows chemotherapy
and other treatments to find and destroy cancer cells … "
