Unveiling Fluoxetine as a Repurposed Drug for Glioblastoma: Insights from Real-World Evidence

Glioblastoma (GBM), a highly lethal brain tumor, poses significant challenges in terms of treatment. Despite advancements in understanding its mutational landscape, genomic insights have yet to translate into improved survival rates for the majority of patients. Even with aggressive treatment approaches such as surgical resection, radiotherapy, and temozolomide (TMZ), the prognosis remains grim, with most patients succumbing to the disease within two years.

In collaboration with colleagues at Stanford Medicine, our research took a groundbreaking approach, utilizing real-world data (RWD) and applying pharmacoepidemiological methods. This led to the discovery of Fluoxetine, an antidepressant, as a repurposed drug that has shown promising results in significantly improving survival rates among glioblastoma patients. This breakthrough opens up new avenues for therapeutic interventions in the treatment of this challenging disease. By leveraging advanced computational techniques, we identified a potential new treatment strategy for GBM using Fluoxetine, a safe and FDA-approved drug with a known molecular mechanistic basis.

To complement our experimental findings, we conducted an analysis of the IBM MarketScan claims database spanning from 2003 to 2017. Through stringent criteria, we identified a group of 238 adult GBM patients who received standard care treatments, including chemotherapy with temozolomide, radiation, and surgical resection. Among these patients, a subset was coincidentally also taking Fluoxetine or one of three other selective serotonin reuptake inhibitors (SSRIs) drugs. Our analysis of real-world data revealed significantly increased survival rates in GBM patients treated with Fluoxetine, a result not observed in patients treated with other three SSRI antidepressants. These findings strongly support the repurposing of Fluoxetine as a potentially safe and promising therapy for GBM patients, warranting prospective randomized clinical trials.

Our study, showcasing these significant findings, was published in Cell Reports on November 2, 2021.

Bi J, Khan A, Tang J, Armando AM, Wu S, Zhang W, Gimple RC, Reed A, Jing H, Koga T, Wong IT. Targeting glioblastoma signaling and metabolism with a re-purposed brain-penetrant drug. Cell reports. 2021 Nov 2;37(5).