A common class of antidepressant medications might be even more useful than we thought. Research out today suggests that selective serotonin reuptake inhibitors, or SSRIs, can fend off cancer and boost the immune system’s defenses against it.
Scientists at the University of California, Los Angeles, led the study, published in Cell. In mice and other lab experiments, they found that SSRIs shrunk a variety of cancers, improved the immune system’s ability to kill cancer cells, and bolstered the effectiveness of immunotherapy. The researchers now hope to conduct clinical trials of SSRIs for cancer in humans.
Serotonin, a hormone with many important functions, has a complicated relationship with cancer. While it appears to promote the growth of certain tumor types, it also seems to enhance our immune response to cancer. Accordingly, scientists have hoped that existing drugs that interact with serotonin, including many antidepressants, could be repurposed to fight cancer.
Several years ago, the UCLA researchers published a study showing MAO inhibitors—early generation antidepressants that regulate serotonin by inhibiting MAO—had an anticancer effect in mice. But these older drugs can cause serious side effects and interact badly with many other drugs or foods. So the researchers next decided to see if they could find a similar effect by targeting a different protein that interacts with serotonin, SERT. And as luck would have it, we already have existing and safer drugs that can inhibit SERT, the SSRIs.
The researchers used SSRIs on mouse and human models of several different cancers (some mice were given cancers derived from human cells, for instance): melanoma, breast, prostate, colon, and bladder cancer. On average, the treatment reduced the size of these tumors by more than 50%. Looking closer, the team also found that SSRIs appeared to make certain immune cells—killer T cells—better at recognizing and killing cancer cells.
“It turns out SSRIs don’t just make our brains happier; they also make our T cells happier—even while they’re fighting tumors,” said senior study researcher Lili Yang, a professor of microbiology, immunology and molecular genetics at UCLA, in a statement from the university. “SSRIs made the killer T cells happier in the otherwise oppressive tumor environment by increasing their access to serotonin signals, reinvigorating them to fight and kill cancer cells.”
Yang and her team then paired SSRIs with another treatment that boosts the immune system’s response against cancer, immune checkpoint blockade (ICB) therapy; these drugs work by inhibiting certain proteins that normally keep immune cells from attacking tumors. In tests with mice, the combination further shrunk melanoma and colon cancer tumors, and in some cases, it even seemed to completely eradicate the cancer.
So far, the findings come from mice and other lab experiments, so we’re still a long way from SSRIs being the next big thing in cancer treatment. But the fact that these drugs are already approved to treat depression is an added boon, the authors say. Compared to experimental treatments, for instance, it would take much less money and resources to develop and potentially win approval of SSRIs for cancer.
UCLA, on behalf of the lead researchers, has filed a patent covering their combination approach, and the team is next looking to put their hypothesis to the test in an actual human trial.
“Our goal is to design a clinical trial to compare treatment outcomes between cancer patients who take these medications and those who do not,” said Yang, also a researcher at UCLA’s Goodman-Luskin Microbiome Center and the Parker Institute for Cancer Immunotherapy.
With any luck, the same drugs that help ward off the blues can also become part of our arsenal against cancer.
