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Psychotropic agents, especially SSRIs and TCAs, have been explored for cancer treatment. Fluoxetine shows distinct anticancer mechanisms beyond serotonin signaling, including oncolytic effects demonstrated in vitro and in vivo as monotherapy or combined with temozolomide or radiotherapy.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/beyond-psychotropic-potential-repurposing-of-fluoxetine-toward-cancer-therapy/341373/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/beyond-psychotropic-potential-repurposing-of-fluoxetine-toward-cancer-therapy/341373.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is drug repurposing and why is it considered advantageous?","Question",{"text":113,"@type":114},"Drug repurposing rebrands an existing drug for a new indication. It is considered beneficial because it can shorten discovery timelines and reduce costs while leveraging already-known pharmacokinetic and toxicity profiles.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does fluoxetine (FLX) relate to cancer therapy?",{"text":118,"@type":114},"FLX has shown oncolytic effects through mechanisms distinct from its primary serotonergic activity. 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Kadasah 1, Abdulaziz M. S. Alqahtani 1, Abdullah Alkhammash 2,* and Mohamed O. Radwan 3, *  \nCitation: Kadasah, S.F.; Alqahtani, A.M.S.; Alkhammash, A.; Radwan, M.O. Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy. Int. J. Mol. Sci. 2024, 25, 6314. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms25126314](10.3390/ijms25126314)  \nAcademic Editor: George Mihai Nitulescu  \nReceived: 16 May 2024  \nRevised: 5 June 2024  \nAccepted: 5 June 2024  \nPublished: 7 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Biology, Faculty of Science, University of Bisha, P.O. Box 551, Bisha 61922, Saudi Arabia  \n2 Department of Pharmacology, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia  \n3 Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan  \n* Correspondence: [alkhammash@su.edu.sa](alkhammash@su.edu.sa) (A.A.); [mohamedradwan@kumamoto-u.ac.jp](mohamedradwan@kumamoto-u.ac.jp) (M.O.R.)  \nAbstract: Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood–brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR) . We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer.  \nKeywords: fluoxetine; cancer; repurposing; multidrug resistance (MDR)  \n1. Introduction  \nDrug repurposing or repositioning represents an attractive approach for finding new applications for old drugs [1,2] . This kind of drug recycling introduces a batch of pros, including a shorter production time by eliminating Phase I clinical trials and a lower costas a consequence in comparison to de novo drug discovery [1] . A pronounced merit of repurposing is that the pharmacokinetic and toxicity profiles of the repurposed entities were already identified. Previously, repurposing was dependent on serendipity; however, recently, it has been based on advanced omics technologies and computational tools [3] . One of the most outstanding examples is aspirin repurposing from a ","cbCaivuflkqFB3wl","https://ap.wps.com/l/cbCaivuflkqFB3wl","pdf",1175284,18,"English","# Abstract\n# 1. Introduction\n## Drug repurposing rationale and advantages\n## Cancer burden and limitations of current therapies\n## Examples of repurposed drugs and research trends\n# Keywords","[{\"question\":\"What is drug repurposing and why is it considered advantageous?\",\"answer\":\"Drug repurposing rebrands an existing drug for a new indication. It is considered beneficial because it can shorten discovery timelines and reduce costs while leveraging already-known pharmacokinetic and toxicity profiles.\"},{\"question\":\"How does fluoxetine (FLX) relate to cancer therapy?\",\"answer\":\"FLX has shown oncolytic effects through mechanisms distinct from its primary serotonergic activity. It can penetrate the blood–brain barrier and has been tested in vitro and in vivo, including as monotherapy and in combination with temozolomide or radiotherapy.\"},{\"question\":\"What evidence is highlighted for combining FLX with other treatments?\",\"answer\":\"The review summarizes synergistic combinations such as FXR/temozolomide for glioblastoma and FXR/raloxifene for breast cancer, and also describes attempts to load FLX onto carriers to improve safety and efficacy against cancer cells.\"}]","Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy | PDF",1790041673,45]