مقالات پذیرفته شده کنگره

  • Transcriptome-Driven Repurposing of Approved Drugs for Cervical Cancer: A Connectivity Map Approach

  • Bahareh Mahmoudi,1,* Fatemeh Ghaeini,2 Parsa Kameli Gelyerdi,3 Mohammad Hossein Mostafavi,4 Amirsajad Jafari,5
    1. Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
    2. Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.
    3. Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.
    4. Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
    5. Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran


  • Introduction: cervical cancer remains one of the most common malignacies in women worldwide,Drug repurposing offers a rapid and cost-effective aiternative to do novo drug discovery.This study animed to identify existing approved drugs that can mimic the gene expression signature induced by doxorubicin in cervical cancer cells.
  • Methods: A differential gene expression signature was derived from HeLa cervical cancer cells.treat with doxorubicin using the publicly available dataset GSE160234(GEO/NCBI).Differential expression analysis was performed using GEO2R with Bonferroni adjustment for p-values,auto-detect log transformation,limma precision weights and force normalization.Genes with adjusted p-value<0.01 and |log2 fold change|>1 were select.The significant gene signature was queired 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,ceritinib(an ALK tyrosine kinase inhibitor) was prioritized due to its full FDA approval and estabilished clinical use in ALK-positive non_small cell lung cancer.Other candidates included the HDAC inhibitors romidepsin and vorinostat as well as the cardiac glycosides digoxin and digitoxin.
  • Conclusion: Ceritinib represents a promising candidate for further investigation in cervical cancer based on transcriptomic similarity to doxorubicin.Experimental validation through in vitro and in vivo studies is required.This computational approach demonstrates a rapid and systematic strategy for repurposing approved drugs.
  • Keywords: Drug repurposing,Cervical cancer,Doxorubicin,Ceritinib,GEO.

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