In a study conducted, antidepressants slowed the growth of pancreatic and colon cancers in mice, and when combined with immunotherapy, they stopped cancer growth long-term.
Researchers at the University of Zurich and University Hospital Zurich have found that Selective Serotonin Reuptake Inhibitors (SSRIs) or other drugs that lower peripheral serotonin levels can slow cancer growth in mice.
Data revealed that, in some cases, the tumors disappeared. Their findings will now be tested in human clinical trials.
This research study was led by Pierre-Alain Clavien, MD, PhD, FACS and Anurag Gupta, MSc, PhD, who discovered the role that serotonin plays in tumor cell resistance. Cancer cells use serotonin to increase the production of a molecule that is immunoinhibitory, which is known as as PD-L1.
"This molecule then binds to killer T cells, a specific type of immune cell that recognizes and eliminates tumor cells and deems them dysfunctional. The cancer cells can therefore avoid being destroyed by the immune system", according to the report of the study by the University of Zurich.
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 said.
PD-L1 is also the target of modern immunotherapies known as immune checkpoint inhibitors. The researchers used mice subjects to test a combination immunotherapy treatment, which increases the activity of killer T-cells, and drugs that reduce peripheral serotonin.1
The involvement of serotonin in carcinogenesis was previously known. However, until now, the underlying mechanisms had remained unknown. Now, researchers at the University of Zurich and University Hospital Zurich have shown that SSRIs can also slow cancer growth in mice.
Although effective treatments, such as targeted antibodies or immunotherapies, are currently available, many patients with advanced-stage tumors such as colon or pancreatic cancer have negative outcomes within years of diagnosis. One issue is that tumor cells can become resistant to the drugs over time and are therefore no longer recognized by the immune system.
The results of the study revealed that cancer growth was suppressed in the animal models over the long-term, and in some mice the tumors fully disappeared.1