The Effect of Serotonin Reuptake Inhibitors in Metastatic Colorectal Cancer

Colon cancer, also called colorectal cancer, is a type of cancer that starts in the colon, which is a part of the digestive system. Colon cancer remains the second most common cause of cancer death in the United States with more than 52,000 deaths in 2023. In the past decade, there have been few improvements in the way colon cancer is treated. The Yang Engineering Immunity Lab at University of California, Los Angeles (UCLA) tested in mice, the possibility of using antidepressants (medications that help treat depression and some other mental health conditions) as part of cancer treatment.

Dr. Yang's team found that levels of Monoamine Oxidase A (MAO-A), which is an enzyme which breaks down serotonin (a chemical messenger that plays a role in regulating mood, emotions, and happiness) go up in certain immune cells when they're fighting cancer, as well as in other cells that help tumors grow. In people with colorectal cancer, higher levels of MAO-A were linked to weaker immune response and worse outcomes.

When they tested these depression medicines such as Selective Serotonin Reuptake Inhibitor.(SSRI) antidepressants, drugs that work by increasing the levels of serotonin, on mice with tumors, they found that the tumors grew slower, especially when the immune system was strong. This suggests that these medicines could be used to help fight colorectal cancer in people too. Given that antidepressants are inexpensive and have few side effects, in this study, we aim to be the first to test this in patients with colon cancer.

Immunotherapy uses your own immune system to help fight cancer. We believe that antidepressants will change "cold" tumors that do not respond to immunotherapy, like colon cancer, into "hot" tumors that do respond. This is a study that looks back at previously collected clinical trial data to explore the outcomes of patients who were on antidepressants while receiving other, more standard, cancer treatments. The hope is that we see improved outcomes in those patients on antidepressants and that it will support further studies that incorporate them into cancer treatment.