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  • Transcriptome-Driven Repurposing of Approved Drugs for Pancreatic Ductal Adenocarcinoma: A Connectivity Map Approach

  • parsa kameli gelyerdi,1 Mohammad Hossein Mostafavi,2 Fatemeh Ghaieni,3 Bahareh Mahmoudi,4,*
    1. DVM Student, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
    2. DVM Student, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
    3. DVM Student, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
    4. Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran


  • Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Drug repurposing offers a rapid alternative to de novo drug design and discovery. This study aimed to identify existing drugs that can reverse or mimic the gene expression signature of approved treatments.
  • Methods: A gene expression profile was derived from PDAC cells treated with Gemcitabine, using dataset GSE153460 from the Gene Expression Omnibus (GEO/NCBI). The resulting significant gene signature was uploaded to the Connectivity Map platform (www.clue.io). Drugs with a high connectivity score (TAS > 0.8 and TAG > 0) were selected as candidates for repurposing.
  • Results: The analysis yielded five drugs with transcriptional signatures that most closely matched the input profile: vorinostat (HDAC inhibitor), MG-132 (proteasome inhibitor), topotecan (topoisomerase I inhibitor), CGP-60474 (CDK/PKC inhibitor), and bortezomib (proteasome inhibitor). These compounds are predicted to induce a cellular state similar to that produced by Gemcitabine in PDAC cells.
  • Conclusion: The five identified drugs represent mechanistically diverse candidates that could potentially suppress PDAC proliferation. However, in vitro and in vivo validation is required. Nevertheless, this computational approach demonstrates a rapid and less-biased strategy for repurposing approved or investigational drugs for aggressive and lethal malignancies, such as PDAC.
  • Keywords: Connectivity Map; PDAC; Gemcitabine; GEO; Bioinformatics; Drug repurposing

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