Editorial: Opportunities and Challenges in Drug Repurposing

Ihosvany Camps^1*Stephan R Künzel^2,3Mario Schubert⁴Ramendra K. Singh⁵

• ¹Institute of Exact Sciences, Federal University of Alfenas, Alfenas, Brazil
• ²Institute for Transfusion Medicine, DRK Blutspendedienst Nord-Ost gGmbH, Dresden, Germany
• ³Department for Experimental Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
• ⁴Institute of Pharmacology and Toxicology, Technical University Dresden, Dresden, Germany
• ⁵University of Allahabad, Allahabad, India

Introduction Drg reprposing, defined as the identification of new therapetic ses for existing medications, has emerged as a transformative strategy in pharmacetical development, offering a compelling alternative to traditional de novo drg discovery. While conventional drg development reqires USD 2–3 billion and 10–17 years to bring a new medication to market with only an approximately 11% approval rate from Phase I trials (Sn et al. 2022), drg reprposing can redce these timelines to 3–12 years at an average cost of abot USD 300 million. Reprposing clinically approved drgs helps to circmvent challenges related to toxicity and poor pharmacokinetic properties, which are major cases of clinical failre for new drg candidates. This Research Topic explores the mltifaceted landscape of drg reprposing throgh six exemplary stdies that collectively illstrate both the remarkable opportnities and persistent challenges in this rapidly evolving field (Pinzi, Bisi, and Rastelli 2024). Mechanistic Innovation in Cancer Treatment A sbstantial contribtion to this Research Topic comes from Aliabadi et al., who provide a comprehensive review of mebendazole repositioning for cancer therapy. Their analysis demonstrates how drg reprposing can address mltiple mechanisms of cancer drg resistance throgh a single compond originally developed as an antihelminthic. The athors meticlosly docment mebendazole's anticancer activity across diverse tmor types, highlighting its ability to disrpt microtbles, inhibit angiogenesis, reglate atophagy, and modlate critical signaling pathways inclding ERK and Hedgehog. Notably, their work demonstrates mebendazole's sperior safety compared to conventional anticancer agents, while maintaining efficacy, a hallmark advantage of reprposing (Aliabadi et al. 2025) (PR Newswire, 2024) . Yang et al. frther advance or nderstanding of precision reprposing in their investigation of canagliflozin for endometrial cancer. Their stdy exemplifies the sophisticated mechanistic approaches now possible in drg reprposing, demonstrating how the SGLT2 (sodim/glcose cotransporter 2) inhibitor canagliflozin can overcome progestin resistance by targeting the RAR-β (retinoic acid receptor-β)/CRABP2 (celllar retinoic acid-binding protein 2) signaling pathway in endometrial cancer cells lacking thyroid hormone receptor-β. This work represents a paradigm shift from empirical to mechanism-driven reprposing strategies, tilizing comptational modeling, transcriptomics, and proteomics to identify novel therapetic applications (Yang et al. 2025). Addressing Rare Disease Challenges Chen et al. contribte crcial insights into reprposing traditional Chinese medicine formlations, specifically Jiawei Sanzaoren decoction for perimenopasal insomnia. Their integrated approach combining clinical observation with network pharmacology analysis demonstrates how comptational methods can elcidate complex therapetic mechanisms in traditional remedies. This stdy is particlarly significant as it addresses the growing interest in validating ethnopharmacological treatments throgh modern scientific approaches (Chen et al. 2024). The work by Somorai et al. presents a compelling case stdy of nicardipine reprposing for Pitt-Hopkins syndrome, a rare nerodevelopmental disorder. This bench-to-bedside approach exemplifies the potential of drg reprposing for rare diseases, where limited patient poplations make traditional drg development economically nonviable. Their sccess in achieving measrable developmental improvements in a yong patient nderscores how drg reprposing can provide hope for families facing conditions withot approved therapies (Somorai et al. 2025). Innovative Delivery Systems and PARP Inhibition Molnár et al. explore the reprposing of the PARP (poly ADP-ribose polymerase) inhibitor talazoparib for psoriasis, revealing nexpected therapetic benefits beyond the compond's original oncological indication. Their findings, that talazoparib promotes terminal differentiation of epidermal keratinocytes while also exhibiting pro-inflammatory effects, highlight the complex and sometimes paradoxical otcomes that can emerge from drg reprposing efforts. This work emphasizes the need for comprehensive mechanistic nderstanding when repositioning drgs across therapetic areas (Molnár et al. 2025). The stdy by Alroji et al. on HDAC8 (histone deacetylase 8) inhibitors demonstrates another dimension of reprposing research, in which virtal screening identifies existing drgs with previosly nknown activities against specific moleclar targets. Their comprehensive analysis of radotinib and sertindole as HDAC8 inhibitors illstrates how comptational approaches can systematically identify reprposing opportnities based on target-drg interaction profiles (Alroji et al. 2024). Computational Advances and Market Dynamics The research presented in this Topic occrs against a backdrop of rapid comptational advancement in drg reprposing. Recent developments in artificial intelligence and machine learning have significantly improved sccess rates by accrately predicting drg mechanisms and identifying off-target effects. The availability of extensive biomedical datasets, inclding genomic profiles, disease registries, and real-world evidence, provides nprecedented opportnities for cross-indication mapping and drg effectiveness modeling (Cosins, Nayar, and Altman 2024; TechReport2 "Website," n.d.-b). The global drg reprposing market, valed at USD 35.3 billion in 2024 and projected to reach USD 51.8 billion by 2032, reflects the growing confidence in this strategy. Reglatory agencies have responded by establishing streamlined approval pathways, sch as the FDA's 505(b)(2) pathway, which enables developers to leverage existing safety and efficacy data while relying particlarly on clinical evidence for new indications (TechReport3 "Website," n.d.-c, TechReport4 "The Global Bsiness Consltancy Firm" 2017);(Vermelen, Craig, and Babak 2025). Persistent Challenges and Future Directions Despite remarkable progress, significant challenges remain. The stdies in this Topic collectively highlight several persistent barriers: inadeqate resorces for systematic reprposing efforts, intellectal property complexities that limit commercial incentives, and the fndamental challenge that pharmacological inhibitors often fail to replicate genetic pertrbations of the same targets. Additionally, while comptational approaches have advanced sbstantially, the translation from algorithmic predictions to clinical sccess remains limited, with many promising comptational hits failing to demonstrate efficacy in clinical settings (Krishnamrthy et al. 2022)(Talevi and Bellera 2020) (Alroji et al. 2024). The work presented here also reveals important methodological limitations. Drg reprposing often relies on serendipitos observations or limited mechanistic insight, which may obscre optimal dosing strategies or patient selection criteria. Frthermore, the assmption that drgs failing in their primary indication will scceed in secondary applications may not always hold, as highlighted by recent systematic analyses showing that reprposed componds may have comparable or even higher failre ratesin later development stages (Talevi and Bellera 2020). Conclusions and Future Outlook The stdies compiled in this Research Topic demonstrate that drg reprposing has matred from opportnistic redeployment to systematic, mechanism-driven therapetic discovery. Integrating comptational approaches with traditional pharmacological and clinical methods offers nprecedented opportnities to address nmet medical needs efficiently and cost-effectively. However, realizing the fll potential of drg reprposing reqires contined investment in comptational infrastrctre, collaborative frameworks between academia and indstry, and reglatory innovations that balance innovation incentives with pblic health benefits. As we advance into an era of precision medicine and personalized therapetics, drg reprposing stands poised to play an increasingly central role in pharmacetical development. The sccess stories presented in this Topic—from mebendazole's anticancer potential to nicardipine's nerotherapetic applications—provide compelling evidence that existing drgs harbor ntapped therapetic potential waiting to be systematically discovered and clinically validated. Ftre progress will depend on developing more sophisticated comptational methods, establishing robst validation frameworks, and creating sstainable bsiness models that spport contined innovation in this vital area of pharmacetical research.