SSRIs Inhibit Crucial Cancer Mechanism, Slowing Tumor Growth Rate

Researchers at the University of Zurich have shown that SSRIs or other drugs that lower peripheral serotonin levels can also slow cancer growth in mice. Their findings were published in Science Translational Medicine. 

“Drugs that are already approved for clinical use as antidepressants could help improve treatment of hitherto incurable pancreatic and colorectal cancers,” says researcher Pierre-Alain Clavien. The research group led by Clavien and Anurag Gupta has discovered the role serotonin plays in this tumor cell resistance mechanism.

Cancer cells use serotonin to boost the production of PD-L1. When this immunoinhibitory molecule binds to killer T cells it renders them dysfunctional. 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 the next step, the researchers tested a dual treatment approach in mice: They combined immunotherapy 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,” Clavien concludes.