Widely Used Antidepressants Show Promise in Cancer Therapy
Antidepressants are doing more than lifting moods – they may also enhance cancer treatment.
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New research, conducted by scientists at the University of California – Los Angeles Health Sciences (UCLA), shows a widely used antidepressant could help the immune system fight cancer.
The study, published in Cell, demonstrated that selective serotonin reuptake inhibitors (SSRIs) enhanced the ability of T cells to fight cancer, in addition to suppressing tumor growth across a range of cancer types in both mouse and human models.
Repurposing antidepressants could improve cancer outcomes
In the US, according to the Centers for Disease Control and Prevention, one in eight adults takes antidepressants – with SSRIs (e.g., ProzacTM (fluoxetine) and CelexaTM (citalopram)) being the most commonly prescribed. These drugs increase levels of the neurotransmitter serotonin – the “happy hormone” – in the brain by blocking the activity of serotonin transporters (SERTs), therefore preventing serotonin reuptake.
Serotonin is best known for its role in the brain; however, it also plays a critical role in other processes, including digestion, metabolism and immune activity.
In 2021, the researchers found that immune cells isolated from tumors had higher levels of serotonin-regulating molecules. They reported that T cells produce monoamine oxidase-A (MAO-A) when they recognize tumors, which makes it harder for them to fight cancer. Treating mice with melanoma and colon cancer using MAO inhibitors (MAOIs) — the first class of antidepressant drugs to be invented — helped T cells attack tumors more effectively.
Monoamine oxidase-A
MOA-A is an enzyme that breaks down serotonin and other neurotransmitters, including norepinephrine and dopamine.
However, due to the safety concerns of MAOIs, including serious side effects and interactions with certain foods and medications, the team turned its attention to a different serotonin-regulating molecule, SERT.
“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 Dr. Lili Yang, senior author of the new study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
“Unlike MAO-A, which breaks down multiple neurotransmitters, SERT has one job – to transport serotonin,” explained Dr. Bo Li, first author of the study and a senior research scientist in the Yang lab. “SERT made for an especially attractive target because the drugs that act on it – SSRIs – are widely used with minimal side effects.”
How SSRIs could boost the effectiveness of cancer therapies
Yang and her team tested SSRIs in both mouse and human tumor models of melanoma, breast, prostate, colon and bladder cancer. They found that SSRI treatment reduced average tumor size by over 50% and made killer T cells more effective at fighting and killing cancer cells.
“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,” said Yang, who is also a professor of microbiology, immunology and molecular genetics and a member of the UCLA Health Jonsson Comprehensive Cancer Center.
To build on these results, the team also investigated whether combining SSRIs with existing cancer therapies could improve treatment outcomes.
They investigated a combination of an SSRI and anti-PD-1 antibody — a common immune checkpoint blockade (ICB) therapy — in mouse models of melanoma and colon cancer.
Immune checkpoint blockade therapies
ICB therapies work by blocking immune checkpoint molecules that normally suppress immune cell activity, allowing T cells to attack tumors more effectively.
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The results were striking: the combination of SSRIs and anti-PD-1 antibodies reduced tumor size in all treated mice and even achieved complete remission in some cases.
“ICBs are effective in fewer than 25% of patients,” said James Elsten-Brown, a graduate student in the Yang lab and co-author of the study. “If a safe, widely available drug like an SSRI could make these therapies more effective, it would be hugely impactful.”
Existing drugs could fast-track cancer therapies
To confirm these findings from mouse and human tumor models, the team will investigate whether cancer patients taking SSRIs have better outcomes – especially those receiving ICB therapies.
“Since around 20% of cancer patients take antidepressants – most commonly SSRIs – we see a unique opportunity to explore how these drugs might improve cancer outcomes,” said Yang. “Our goal is to design a clinical trial to compare treatment outcomes between cancer patients who take these medications and those who do not.”
Using existing FDA-approved drugs could speed up the process of bringing new cancer treatments to patients, making this research especially promising.
“Studies estimate the bench-to-bedside pipeline for new cancer therapies costs an average of $1.5 billion,” she 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.”
Reference: Li B, Elsten-Brown J, Li M, et al. Serotonin transporter inhibits antitumor immunity through regulating the intratumoral serotonin axis. Cell. 2025. doi: 10.1016/j.cell.2025.04.032
This article is a rework of a press release issued by the University of California - Los Angeles Health Sciences. Material has been edited for length and content.
