Targeting the immune system to fight cancer has been in the works for over a decade, and thanks to its precise, personalized approach, it’s poised to shape the future of oncology. As our understanding of how immunotherapy can be used against cancer grows, scientists are now reconsidering existing drugs, particularly those that affect the immune system, for their potential role in cancer treatment.
Alongside well-established medications like aspirin, showing potential to help the immune system combat cancer, researchers are now turning their attention to antidepressants — and the results are looking promising.
A team from UCLA recently published a study in Cell showing how SSRIs, a widely prescribed class of antidepressants, can help the immune system suppress tumor growth across various cancer types. So instead of developing entirely new drugs, could the key lie in repurposing ones we already have?
“These drugs have been widely and safely used to treat depression for decades, so repurposing them for cancer would be a lot easier than developing an entirely new therapy,” said senior study author Lili Yang, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, in a press statement.
The Role of Antidepressants
SSRIs, or selective serotonin reuptake inhibitors, work by increasing levels of serotonin, a neurotransmitter associated with mood and focus, and by blocking the serotonin transporter (SERT), which typically regulates how much serotonin is available outside our cells. In people with depression, serotonin levels in the brain drop significantly — a problem that SSRIs like fluoxetine (Prozac), citalopram (Celexa), and sertraline (Zoloft) help to address.
But serotonin isn’t just about mood. Only about 5 percent of the body’s serotonin is made in the brain. The rest acts as a signaling molecule in many essential bodily functions, including digestion — and, as recent research suggests, immune system regulation.
While earlier lab studies hinted that serotonin might help stimulate T-cells, the immune system’s front-line soldiers, its precise role and potential in immunoregulation remained unclear. That is, until now.
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Antidepressants and Anti-Tumor Potential
Before studying SSRIs, the UCLA team had explored another class of antidepressants called MAO inhibitors (MAOIs), which also increased serotonin levels by blocking an enzyme known as MAO-A. These drugs showed anti-tumor potential, but due to their higher risk of side effects, researchers shifted their focus to SSRIs.
“SERT made for an especially attractive target because the drugs that act on it — SSRIs — are widely used with minimal side effects,” said Bo Li, the study’s first author, in the news release. By using SSRIs to boost serotonin availability, researchers aimed to outmaneuver one of cancer’s suggested strategies: depriving immune cells of the serotonin they need to function effectively.
The results were encouraging. In both mouse and human tumor models of melanoma, breast, prostate, colon, and bladder cancers, SSRI treatment shrank tumors by over 50 precent. The key, according to Yang, was “increasing their access to serotonin,” which in turn enhanced the T-cells’ ability to attack.
Combining with Existing Cancer Treatments
The team also tested whether combining SSRIs with existing cancer treatments could offer even better results. The answer was yes. In follow-up experiments, all mice with melanoma or colon cancer that received both an SSRI and immune checkpoint blockade (ICB) therapy, a treatment designed to overcome the immune-suppressing nature of tumors, experienced significantly reduced tumor sizes.
“Immune checkpoint blockades are effective in fewer than 25 percent of patients,” said study co-author James Elsten-Brown in the press release. “If a safe, widely available drug like an SSRI could make these therapies more effective, it would be hugely impactful.”
Using therapies already deemed safe means fewer regulatory hurdles and faster clinical use.
“Studies estimate the bench-to-bedside pipeline for new cancer therapies costs an average of $1.5 billion,” Yang said. “When you compare this to the estimated $300 million cost to repurpose FDA-approved drugs, it’s clear why this approach has so much potential.”
This article is not offering medical advice and should be used for informational purposes only.
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Having worked as a biomedical research assistant in labs across three countries, Jenny excels at translating complex scientific concepts – ranging from medical breakthroughs and pharmacological discoveries to the latest in nutrition – into engaging, accessible content. Her interests extend to topics such as human evolution, psychology, and quirky animal stories. When she’s not immersed in a popular science book, you’ll find her catching waves or cruising around Vancouver Island on her longboard.
