Tumor growth stopped in mice

Antidepressants show promise in cancer growth inhibition

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.

Image source: Shutterstock/Kateryna Kon

In some cases the tumors disappeared completely, researchers at the University of Zurich (UZH) and University Hospital Zurich (USZ) have found. Their findings, which have been published in the journal Science Translational Medicine, will now be tested in human clinical trials.

Drugs that are already approved for clinical use as antidepressants could help improve treatment of hitherto incurable pancreatic and colorectal cancers

Pierre-Alain Clavien

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.

The involvement of serotonin in carcinogenesis was already known. Until now, however, the underlying mechanisms had remained obscure. Now, researchers at UZH and 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.

Photo
Illustration of immune checkpoint inhibitors in cancer treatment. PD-1 receptor and PD-L1 inhibitors prevent the tumor cell from binding to PD-1 and enable the T cell to be maintained.

Image source: Shutterstock/Kateryna Kon

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.

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.


Source: University of Zurich

28.09.2021

Read all latest stories

Related articles

Photo

Aggressive brain tumour

Glioblastoma can be tricked into 'repairing' itself

Scientists at the University College London (UCL) have made a ‘surprising’ discovery that glioblastoma, an aggressive brain cancer, mimics normal brain repair in white matter, which leads to the…

Photo

A BOLD-100 approach

Novel metallodrug shows promise in tumour treatment

BOLD-100/KP1339 is a ruthenium-based anticancer agent that has been co-developed at the University of Vienna and which has shown promising results in clinical trials in cancer patients. However, the…

Photo

Malignant infantile brain tumours

​Epilepsy drug inhibits brain tumour development

Medication prescribed for a certain type of epilepsy may offer a new method for treating malignant infantile brain tumours. A specific mTOR inhibitor has the ability to cross the blood–brain…

Related products

Sarstedt – Low DNA Binding Micro Tubes

Research Use Only (RUO)

Sarstedt – Low DNA Binding Micro Tubes

SARSTEDT AG & CO. KG
Shimadzu – CLAM-2030

Research Use Only (RUO)

Shimadzu – CLAM-2030

Shimadzu Europa GmbH
Subscribe to Newsletter