In silico analysis for drug repurposing in cholesteatoma: A novel approach to address an unmet medical need

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 bioinformatics platform, for analysis. We employed common pathway enrichment analysis and cross-referenced data from DrugBank and gene list automatically derived for you drug annotations to identify potential medical treatments. Our analysis covered eight high-throughput genetic studies, with extended gene lists available for five of them. Enrichment analysis identified common pathways, including matrix metalloproteinases, interleukins, apoptosis, and the phosphoinositide 3-kinase-AKT pathway, shedding light on both expected and less-studied aspects of cholesteatoma pathogenesis. In addition, the analysis proposed several medications, including anti-tumor necrosis factor-α (TNF-α), zinc, and marimastat, as potential treatments. In conclusion, drug repurposing is a potential cost-effective approach to address the unmet medical need for cholesteatoma management. The identified medications, especially anti-TNFα and zinc, offer promising options. Given the limited research funding in this field, this bioinformatic approach holds great promise, highlighting specific molecular pathways that hold the greatest potential to be implicated in the pathogenesis of cholesteatoma and offering a faster route for future trials to reduce cholesteatoma recurrence.

Keywords

Cholesteatoma / Enrichment pathways / Drug repurposing / Bioinformatics platform

Funding

None.

Conflict of interest

The authors declare no conflict of interest.

References

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