Antidepressants inhibit cancer growth in mice

Date:
September 28, 2021
Source:
University of Zurich
Summary:
Classic antidepressants could help improve modern cancer
treatments. They slowed the growth of pancreatic and colon cancers
in mice, and when combined with immunotherapy, they even stopped
the cancer growth long- term. In some cases the tumors disappeared
completely, researchers have found. Their findings will now be
tested in human clinical trials.



FULL STORY ========================================================================== Classic antidepressants could help improve modern cancer treatments. They slowed the growth of pancreatic and colon cancers in mice, and when
combined with immunotherapy, they even stopped the cancer growth
long-term. In some cases the tumors disappeared completely, researchers
at UZH and USZ have found.

Their findings will now be tested in human clinical trials.


========================================================================== Serotonin is a neurotransmitter that is also known as the happiness
hormone because of its beneficial effects on mood. In depressed people,
the concentration of serotonin in the brain is reduced. The hormone also influences many other functions throughout the body. The majority of
the serotonin is not located in the brain, but is stored in the blood platelets. Serotonin reuptake inhibitors (SSRIs), which are used to
treat depression, increase serotonin levels in the brain but decrease peripheral serotonin in platelets.

SSRIs slow tumor growth The involvement of serotonin in carcinogenesis
was already known. Until now, however, the underlying mechanisms had
remained obscure. Now, researchers at the University of Zurich (UZH)
and University Hospital Zurich (USZ) have shown that SSRIs or other
drugs that lower peripheral serotonin levels can also slow cancer
growth in mice. "Drugs that are already approved for clinical use as antidepressants could help improve treatment of hitherto incurable
pancreatic and colorectal cancers," says Pierre-Alain Clavien, director
of the Department of Surgery and Transplantation.

Although new, effective treatments -- such as targeted antibodies or immunotherapies -- have been available for several years, most patients
with advanced-stage abdominal tumors such as colon or pancreatic cancer
die within a few years of diagnosis. One problem is that the tumor cells
become resistant to the drugs over time and are no longer recognized by
the immune system. Now, the research group led by Pierre-Alain Clavien
and Anurag Gupta has discovered the role serotonin plays in this tumor
cell resistance mechanism.

Without serotonin, the immune system recognizes the cancer cells again
Cancer cells use serotonin to boost the production of a molecule that
is immunoinhibitory, known as PD-L1. This molecule binds to killer T
cells, a specific type of immune cell that recognizes and eliminates
tumor cells, and renders them dysfunctional. The cancer cells thus
avoid being destroyed by the immune system. In experiments with mice,
the researchers were able to show that SSRIs or peripheral serotonin
synthesis inhibitors prevent this mechanism.

"This class of antidepressants and other serotonin blockers cause immune
cells to recognize and efficiently eliminate tumor cells again. This
slowed the growth of colon and pancreatic cancers in the mice,"
Clavien says.

Hope for novel combination therapies PD-L1, via which serotonin
exerts its effect, is also the target of modern immunotherapies, also
called immune checkpoint inhibitors. In a next step, the researchers
tested a dual treatment approach in mice: They combined immunotherapy,
which increases the activity of killer T cells, with drugs that reduce peripheral serotonin. The results were impressive: Cancer growth was
suppressed in the animal models in the long term, and in some mice the
tumors disappeared completely.

"Our results provide hope for cancer patients, as the drugs used are
already approved for clinical use. Testing such drug combinations on
cancer patients in clinical trials can be fast-forwarded due to the
known safety and efficacy of the drugs," says Pierre-Alain Clavien.

========================================================================== Story Source: Materials provided by University_of_Zurich. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Marcel Andre' Schneider, Laura Heeb, Michal Mateusz Beffinger,
Stanislav
Pantelyushin, Michael Linecker, Lilian Roth, Kuno Lehmann,
Udo Ungethu"m, Sebastian Kobold, Rolf Graf, Maries van
den Broek, Johannes vom Berg, Anurag Gupta, Pierre-Alain
Clavien. Attenuation of peripheral serotonin inhibits tumor
growth and enhances immune checkpoint blockade therapy in murine
tumor models. Science Translational Medicine, 2021; 13 (611) DOI:
10.1126/scitranslmed.abc8188 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210928102241.htm

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