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Harnessing Single-Cell RNA-Seq for Computational Drug Repurposing in Cancer Immunotherapy.

Olivia J Cheng1,2, T T T Tran2,3, Y Ann Chen2,3

  • 1Department of Oncological Sciences, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA.

Pharmaceuticals (Basel, Switzerland)
|November 27, 2025
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Summary

This study explores using single-cell RNA sequencing (scRNA-seq) with computational drug repurposing to find new cancer therapies. These methods aim to improve response rates for immune checkpoint inhibitors (ICIs) in difficult-to-treat cancers.

Keywords:
combination therapiesimmune checkpoint inhibitorsimmunotherapysingle-cell RNA sequencingtumor microenvironment

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Area of Science:

  • Oncology
  • Computational Biology
  • Genomics

Background:

  • Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but have limited efficacy in certain cancers like esophageal cancer.
  • Tumor microenvironment heterogeneity and patient variability contribute to low ICI response rates, necessitating novel therapeutic strategies.
  • Drug repurposing offers an efficient alternative to de novo drug development for identifying combination therapies to overcome ICI resistance.

Purpose of the Study:

  • To review computational drug repurposing tools that utilize single-cell RNA sequencing (scRNA-seq) data.
  • To apply scRNA-seq-based tools (scDrug and scDrugPrio) to an esophageal squamous cell carcinoma dataset.
  • To identify potential drug candidates for combination therapy to enhance ICI treatment response.

Main Methods:

  • Leveraging scRNA-seq data for precise targeting of cancer cells and the tumor microenvironment.
  • Utilizing scDrug tool for predicting tumor cell-specific cytotoxicity.
  • Employing scDrugPrio tool to prioritize drugs by reversing gene signatures associated with ICI non-responsiveness.

Main Results:

  • Demonstrated the application of scDrug and scDrugPrio on an esophageal squamous cell carcinoma dataset.
  • Identified potential drug candidates for combination with ICI therapy.
  • Highlighted the utility of scRNA-seq in computational drug repurposing for enhancing ICI efficacy.

Conclusions:

  • Computational drug repurposing using scRNA-seq data is a promising strategy to improve ICI response rates.
  • A multi-faceted approach combining different computational tools enhances drug repurposing effectiveness.
  • Future research should explore multi-omics and spatial transcriptomics for personalized drug discovery in ICI therapy.