UCLA researchers have discovered that selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants used by millions worldwide, may have unexpected cancer-fighting properties. The study, published in the journal Cell, reveals these medications can enhance the immune system's ability to combat various cancer types.
The research team found that SSRIs significantly improved T cells' cancer-fighting capabilities and reduced tumor size by more than half in multiple cancer models. This breakthrough suggests potential for repurposing these widely prescribed medications as adjunct cancer treatments.
SSRIs Enhance T Cell Function Against Cancer
Dr. Lili Yang, senior author and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, explained the surprising mechanism: "It turns out SSRIs don't just make our brains happier; they also make our T cells happier - even while they're fighting tumors."
The researchers tested SSRIs in both mouse and human tumor models representing melanoma, breast, prostate, colon, and bladder cancers. Their findings showed that these antidepressants enhanced the efficiency of killer T cells - specialized white blood cells that identify and destroy cancer cells.
"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," Dr. Yang noted.
From MAO Inhibitors to SSRIs
The research builds on the team's previous work investigating serotonin's role in cancer immunity. In 2021, they discovered that T cells produce monoamine oxidase A (MAO-A), an enzyme that breaks down serotonin, when they recognize tumors. This process appeared to hinder T cells' cancer-fighting abilities.
Initial experiments with monoamine oxidase inhibitors (MAOIs) showed promise in helping T cells attack tumors more effectively. However, MAOIs can cause significant side effects and food interactions, prompting the team to explore alternatives.
"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 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."
Combination Therapy Shows Promise
The team also investigated combining SSRIs with existing cancer immunotherapies. This approach further reduced tumor size in all treated mice, suggesting potential synergistic effects.
While primarily known for their role in regulating brain chemistry, serotonin also influences digestion, metabolism, and immune activity. The UCLA team began exploring serotonin's cancer-fighting potential after noticing that immune cells isolated from tumors had elevated levels of serotonin-regulating molecules.
Future Research Directions
Despite these promising results, the researchers emphasize that additional studies are needed. The team plans to investigate whether cancer patients currently taking SSRIs show better treatment outcomes than those not on these medications.
If confirmed in clinical settings, this research could open new therapeutic avenues for cancer treatment using medications that already have well-established safety profiles. The repurposing of existing drugs represents a potentially faster and more cost-effective approach to developing new cancer therapies.
The study highlights the unexpected connections between neurological and immunological processes, demonstrating how medications developed for one purpose may have beneficial effects in seemingly unrelated conditions.
