A study in mice investigates the potential of an immunotherapy-dietary supplement combo in treating prostate cancer.
- About 13% of cisgender men around the world
will receive a prostate cancer diagnosis in their lifetime.
- Despite improved screening and early detection
methods, about one in 44 men die from prostate cancer.
- Using a mouse model of prostate cancer,
researchers from the University of Notre Dame have now found adding a
pre-ketone supplement to immunotherapy may make it more efficient in
treating this form of cancer.
About 13% of
cisgender men worldwide will receive a diagnosis of prostate cancer during
their lifetime, making it the second
most commonly diagnosed cancer globally.
Despite
improved screening and early detection methods, more advanced
stages of prostate cancer can be difficult
to treat — scientists estimate about one in 44 men will die of prostate cancer.
Now,
a new study from researchers at the University of Notre Dame — published
in Cancer
Research — has found
that adding a component of the keto diet called
a pre-ketone supplement may help a newer type of
prostate cancer treatment called immunotherapy be
more efficient in treating the cancer, via a mouse model.
Immunotherapy
for prostate cancer: Does it work?
Immunotherapy
is a treatment that uses the body’s immune system to fight cancer.
There
are currently two types of immunotherapy available for prostate cancer
— cancer vaccines and immune checkpoint inhibitors.
“Immunotherapy, through
inhibiting T-cell immune checkpoint pathways — PD1 or
CTLA4 — has revolutionized many [therapies for] other cancer types
[too],” Xin
Lu, PhD, the John M. and Mary Jo Boler collegiate associate professor
in the Department of Biological Sciences at the University of Notre Dame, IN,
and corresponding author of this study explained to Medical News Today.
“However,
advanced prostate cancer remains resistant to it,” he added.
“This
is likely due to an increase of pro-tumor immune cells coupled with
insufficient tumor-specific antigens that the immune system can recognize to
kill the cancer cells,” Lu explained. “Therefore, we need to find new ways to
sensitize prostate cancer to immunotherapy.”
Why use a
pre-ketone supplement with immunotherapy?
For
this study, researchers examined what would happen if they added a pre-ketone
supplement to immunotherapy for prostate cancer.
According to Sean
Murphy, PhD candidate in the Lu Lab in the Department of Biological
Sciences at the University of Notre Dame and first author of this study, the
idea to use a pre-ketone supplement came from an observation that an epigenetic
drug — so-called HDAC
inhibitor — was able to sensitize prostate cancer models to
immunotherapy.
There
were also previous reports that ketogenic diets can produce ketone body beta-hydroxybutyrate
(BHB), which has HDAC inhibitor-like properties.
“We
tried both [a] ketogenic diet and pre-ketone BHB-generated supplement, with the
latter being potentially more practical for a patient to use in a clinic,”
Murphy told us. “Another reason to use [a] pre-ketone supplement is to
determine if the presence of BHB was sufficient to enhance immunotherapy in the
mouse models.”
“With
pre-ketone supplement showing an even better response in our study, we conclude
that the presence of BHB, rather than extremely low carbohydrate, was the key
factor to drive better response to immunotherapy,” he added.
Combo
effective against prostate tumors in 23% of mice
Lu,
Murphy, and their colleagues explored their hypothesis via a mouse model of
prostate cancer. They divided the mice into six groups.
Three
of the groups received only immunotherapy, only a keto diet, or only a
pre-ketone supplement. Two more groups were given a combination of the keto
diet and immunotherapy or the pre-ketone supplement plus immunotherapy. The
sixth group was the control group.
At
the study’s conclusion, the researchers found there was no change in tumors in
the immunotherapy-only group.
Both
the pre-ketone-supplement-only approach, and the combination of keto diet and
immunotherapy reduced cancer tumors and extended the lives of the mice.
Overall, the scientists
found that the group with the combination of pre-ketone supplement and
immunotherapy had the best outcomes, with 23% of the mice becoming tumor-free.
How does a
pre-ketone supplement boost immunotherapy?
“The
pre-ketone supplement does two things to enhance immunotherapy,” Lu explained.
“First, it makes cancer cells more detectable to the
immune system by increasing the presentation of molecular features on the
surface of cancer cells. Second, ketone body from the supplement, together with
the immunotherapy, elicit special metabolic and molecular effects on immune
cells so the cells are doubly stimulated to attack the cancer, potentially
clearing it.”– Xin Lu, PhD
“The
23% cure rate certainly brought a lot of hope at this preclinical stage,
because patients with castration-resistant prostate cancer have no curative
treatment in the clinic,” Murphy said.
“Of
course, we also understand 23% is not a high number. There is still room to
increase this number by optimizing the combination and possibly adding another
therapy,” he admitted.
Would
following a keto diet lower prostate cancer risk?
MNT also spoke with Wael
Harb, MD, a board-certified hematologist and medical oncologist at
MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain
Valley, CA, about this study.
Harb,
who was not involved in this research, said he found the idea of combining a
ketogenic diet or ketone supplement and immunotherapy to potentially enhance
the efficacy of checkpoint blockade therapy in prostate cancer intriguing.
“As
we all know, prostate cancer has been notoriously resistant to therapies, but
the use of immunotherapy has shown us more success in other types of cancerl,
such as melanoma and lung cancer,” he
noted.
However,
to anyone thinking that following the keto diet or adding a pre-ketone
supplement to their diet might help decrease their prostate cancer risk, Harb
said to remember the human body is complex and when you do a study like this,
it does not necessarily translate to the keto diet being able to treat cancer.
“The study, I would say,
at best at this point [in] time raises the interest in exploring that
[possibility] clinically, but it’s not anywhere close to making a
recommendation for patients as far as to fight cancer or prevent cancer,” Harb
cautioned.
“I
would like to see a clinical trial — moving from animal models to human
clinical trials is essential in developing efficacy and safety and that’s
something really needed. [And] if this is true for prostate cancer, it might be
true for other cancers — we need to look into other tumor types,” he added.
“And
I think we need to look into the diet even more carefully — how much ketosis would
we need to induce?” Harb wondered.
He
also emphasized that:
“We have to be careful for patients with cancer — we
don’t want them to lose weight. The ketogenic diet can lead to weight loss, and
weight loss can be detrimental for somebody who has cancer. […] So can we
induce [a] ketogenic rate without making them lose weight? There needs to be
some middle ground where we’re able to maintain weight and muscle mass while we
are helping overcome the resistance to immunotherapy.”
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