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.
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 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 the senior author.
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 has discovered the role serotonin plays in this tumor cell resistance mechanism.
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,” the author 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 the senior author.
https://www.media.uzh.ch/en/Press-Releases/2021/antidepressants-cancer.html
https://www.science.org/doi/10.1126/scitranslmed.abc8188
Inhibiting peripheral serotonin to reduce cancer growth
- 1,549 views
- Added
Edited
Latest News
Dissection of the schizophr…
By newseditor
Posted 26 May
Protease action on controll…
By newseditor
Posted 25 May
Maternal inflammation activ…
By newseditor
Posted 25 May
How cells deal with extra c…
By newseditor
Posted 25 May
Flicker stimulation modulat…
By newseditor
Posted 25 May
Other Top Stories
Elevated love hormone levels and higher satisfaction with life in y…
Read more
Synthetic red blood cells to carry drugs!
Read more
Why some older adults remember better than others
Read more
Mechanism of sperm maturation!
Read more
Facial and scene recognition areas of brain identified!
Read more
Protocols
Spatially resolved lipidomi…
By newseditor
Posted 24 May
Efficient expansion and CRI…
By newseditor
Posted 21 May
Massively parallel in vivo…
By newseditor
Posted 20 May
Breast cancer-on-chip for p…
By newseditor
Posted 16 May
Methods for making and obse…
By newseditor
Posted 15 May
Publications
Toward an interventional sc…
By newseditor
Posted 26 May
Cryo-EM reveals that iRhom2…
By newseditor
Posted 25 May
Fetal brain response to mat…
By newseditor
Posted 25 May
Children born after assiste…
By newseditor
Posted 25 May
Macrophage-induced integrin…
By newseditor
Posted 25 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar