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  • Identification of Candidate Drugs for Breast Cancer via Transcriptomic Signature Matching Using Connectivity Map

  • Fatemeh Ghaeini,1 Parsa Kameli Gelyerdi,2 Mohammad Hossein Mostafavi,3 Bahareh Mahmoudi,4 Amirsajad Jafari,5,*
    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
    5. Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran / Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran


  • Introduction: Breast cancer remains one of the most common malignancies worldwide. Drug repurposing offers a rapid and cost-effective alternative to de novo drug discovery. This study aimed to identify existing drugs that can mimic the gene expression signature induced by standard chemotherapy.
  • Methods: A differential gene expression signature was derived from MCF7 breast cancer cells treated with doxorubicin using the publicly available dataset GSE244574 (GEO/NCBI). Differential expression analysis was performed using GEO2R. The analysis settings included Holm adjustment for p-values, auto-detect log transformation, limma precision weights, and force normalization. Genes with adjusted p-value < 0.0001 and |log2 fold change| > 5 were selected. The significant gene signature was then queried in the Connectivity Map platform (clue.io). Compounds with high connectivity scores were selected as potential repurposing candidates.
  • Results: The analysis identified several compounds with strong transcriptional similarity to the doxorubicin-induced signature. Among them, topotecan (a topoisomerase I inhibitor) showed the highest clinical relevance. Other candidates included MG-132, thapsigargin, emetine-HCl, and wortmannin. Topotecan was prioritized due to its full FDA approval and established use in cancer therapy.
  • Conclusion: Topotecan represents a promising candidate for further investigation in breast cancer. Experimental validation through in vitro and in vivo studies is required. This computational approach demonstrates a rapid strategy for repurposing approved drugs based on transcriptomic similarity.
  • Keywords: Connectivity Map; Breast cancer; Doxorubicin; Bioinformatics; Drug repurposing

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