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INNOSC Theranostics

                                                  and Pharmacological Sciences




                                        SHORT COMMUNICATION
                                        In silico analysis for drug repurposing in

                                        cholesteatoma: A novel approach to address an
                                        unmet medical need



                                                        1
                                        Ioannis M. Vlastos * , Mohannad Almomani 1  , John Hajiioannou 2  ,
                                                        1
                                        Nikolaos Drimalas , and Kalliopi Gkouskou 3
                                        1 Department of Otolaryngology-Head and Neck Surgery, Evangelismos Hospital, Athens, Greece
                                        2 Department of Otolaryngology-Head and Neck Surgery, Medical School and University Hospital of
                                        Thessalia, Larissa, Greece
                                        3 Biology and Genetics Lab, School of Medicine, National and Kapodistrian University of Athens,
                                        Athens, Greece



                                        Abstract

                                        Cholesteatoma presents a significant clinical challenge with limited pharmaceutical
                                        treatment options. This paper aims to explore the potential of drug repurposing
                                        for managing cholesteatoma through advanced bioinformatics analysis of high-
                                        throughput  genetic  data.  For  this  purpose,  we  conducted  a  systematic  search  of
                                        published high-throughput genetic studies related to cholesteatoma and used
                                        functional and literature enrichment analysis of multiple sets, a validated web-based
            *Corresponding author:      bioinformatics platform, for analysis. We employed common pathway enrichment
            Ioannis M. Vlastos
            (ivlastos@evaggelismos-hosp.gr)   analysis and cross-referenced data from DrugBank and gene list automatically derived
                                        for you drug annotations to identify potential medical treatments. Our analysis
            Citation: Vlastos IM, Almomani M,
            Hajiioannou J, Drimalas N,   covered eight high-throughput genetic studies, with extended gene lists available
            Gkouskou K. In silico analysis for   for five of them. Enrichment analysis identified common pathways, including matrix
            drug repurposing in cholesteatoma:   metalloproteinases, interleukins, apoptosis, and the phosphoinositide 3-kinase-AKT
            A novel approach to address an
            unmet medical need. INNOSC   pathway, shedding light on both expected and less-studied aspects of cholesteatoma
            Theranostics and Pharmacological   pathogenesis. In addition, the analysis proposed several medications, including anti-
            Sciences. 2025;8(3):107-112.   tumor necrosis factor-α (TNF-α), zinc, and marimastat, as potential treatments. In
            doi: 10.36922/itps.2571
                                        conclusion, drug repurposing is a potential cost-effective approach to address the
            Received: December 29, 2023  unmet medical need for cholesteatoma management. The identified medications,
            Revised: February 17, 2024  especially anti-TNFα and zinc, offer promising options. Given the limited research
                                        funding in this field, this bioinformatic approach holds great promise, highlighting
            Accepted: March 20, 2024
                                        specific molecular pathways that hold the greatest potential to be implicated in the
            Published online: April 11, 2025  pathogenesis of cholesteatoma and offering a faster route for future trials to reduce
            Copyright: © 2025 Author(s).   cholesteatoma recurrence.
            This is an Open-Access article
            distributed under the terms of the
            Creative Commons Attribution   Keywords: Cholesteatoma; Enrichment pathways; Drug repurposing; Bioinformatics
            License, permitting distribution,   platform
            and reproduction in any medium,
            provided the original work is
            properly cited.
            Publisher’s Note: AccScience
            Publishing remains neutral with   1. Introduction
            regard to jurisdictional claims in
            published maps and institutional   Cholesteatoma, a keratinizing epithelial lesion within the middle ear, poses a significant
            affiliations.               clinical challenge due  to the  lack of  pharmaceutical treatments.  At present,  surgical


            Volume 8 Issue 3 (2025)                        107                               doi: 10.36922/itps.2571
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