An Overview of the Potential Use of Selective Serotonin Reuptake Inhibitors (SSRIs) in Cancer Treatment

Cancer is a major health problem and the second leading cause of death worldwide. Chemotherapy remains the mainstay therapeutic option to treat cancer patients, which consists of conventional, hormonal, and/or targeted therapies. However, the significant adverse effects, negative impact on patients' quality of life, and high costs of some medications, as well as the challenges associated with developing new drugs, are prompting the scientific community to seek innovative and alternative treatment strategies. One such strategy is drug repurposing, the use of existing drugs, already approved for other medical conditions for cancer treatment, lev-eraging their known safety and toxicity profiles. Among these groups are the selective seroto-nin reuptake inhibitors (SSRIs) that target serotonin transporter (SERT). In this review, we presented the mechanism of action of SSRIs on the systems biology level, along with their network pharmacology related to protein-protein interactions. We also showed the association of SSRIs and SERT with various diseases, including several types of cancer. Knowing the expression of SERT in cancer and being a target for SSRIs, studies have been investigating the repurposing of SSRIs for cancer treatment. This review also presents a summary of several clinical and preclinical studies that have investigated the use of SSRIs either as single agents or in combination with conventional chemotherapy for cancer treatment, showing promising results. Collectively, they have shown the antiproliferative and growth inhibition effects on cancer cells and/or tumors. We also presented the mechanism(s) of action and pathways these drugs are acting in cancer, along with molecular changes in cellular proteins and enzymes.