Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy

Area of Science:

• Oncology
• Pharmacology
• Drug Discovery

Background:

• Drug repurposing offers a cost-effective and faster alternative to traditional drug discovery.
• Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are psychotropic drugs being investigated for novel therapeutic applications.
• Fluoxetine (FLX), a widely prescribed SSRI, possesses a favorable safety profile and has demonstrated oncolytic properties beyond its serotonergic activity.

Purpose of the Study:

• To review the literature on the repurposing of fluoxetine (FLX) for cancer therapy.
• To highlight the pleiotropic oncolytic roles and molecular mechanisms of FLX against various cancers.
• To explore synergistic combinations and drug delivery strategies for enhanced FLX efficacy in cancer treatment.

Main Methods:

• Literature review of preclinical and clinical studies on fluoxetine (FLX) in cancer.
• Analysis of in vitro and in vivo experimental data.
• Examination of synergistic combinations, including FLX with temozolomide (TMZ) and raloxifene.

Main Results:

• Fluoxetine (FLX) exhibits direct oncolytic effects through diverse molecular mechanisms, independent of its antidepressant action.
• FLX demonstrates efficacy in brain tumors due to its ability to cross the blood-brain barrier.
• Synergistic effects were observed with combinations like FLX/temozolomide for glioblastoma and FLX/raloxifene for breast cancer.
• FLX can overcome multidrug resistance (MDR) in cancer cells.

Conclusions:

• Fluoxetine (FLX) represents a promising repurposed drug for various cancers, including brain tumors.
• Its ability to interrupt cancer proliferation and overcome MDR warrants further clinical investigation.
• Optimizing FLX delivery through pharmaceutical carriers can enhance its safety and efficacy in oncology.