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Updated: Oct 10, 2025
Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data
Annie Wai Yeeng Chai1, Aik Choon Tan2, Sok Ching Cheong3,4
1Translational Cancer Biology Research Unit, Cancer Research Malaysia, Cancer Research Malaysia, 2nd Floor Outpatient Center, Subang Jaya Medical Center, No. 1, Jalan SS12/1A, 47500, Subang Jaya, Selangor, Malaysia.
Abstract:
Effective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking. We exploited the drug response and genomic data of the 28 HNSCC cell lines, screened with 4,518 compounds, from the PRISM repurposing dataset to uncover repurposing drug candidates for HNSCC. A total of 886 active compounds, comprising of 418 targeted cancer, 404 non-oncology, and 64 chemotherapy compounds were identified for HNSCC. Top classes of mechanism of action amongst targeted cancer compounds included PI3K/AKT/MTOR, EGFR, and HDAC inhibitors. We have shortlisted 36 compounds with enriched killing activities for repurposing in HNSCC. The integrative analysis confirmed that the average expression of EGFR ligands (AREG, EREG, HBEGF, TGFA, and EPGN) is associated with osimertinib sensitivity. Novel putative biomarkers of response including those involved in immune signalling and cell cycle were found to be associated with sensitivity and resistance to MEK inhibitors respectively. We have also developed an RShiny webpage facilitating interactive visualization to fuel further hypothesis generation for drug repurposing in HNSCC. Our study provides a rich reference database of HNSCC drug sensitivity profiles, affording an opportunity to explore potential biomarkers of response in prioritized drug candidates. Our approach could also reveal insights for drug repurposing in other cancers.
Insights
This study identifies 886 potential drug repurposing candidates for head and neck squamous cell carcinoma (HNSCC), including targeted therapies and chemotherapy. It highlights EGFR ligands as biomarkers for osimertinib sensitivity, aiding new HNSCC treatment strategies.
Area of Science:
- Oncology
- Pharmacology
- Genomics
Background:
- Head and neck squamous cell carcinoma (HNSCC) lacks effective treatment options.
- Drug repurposing offers a promising avenue for identifying novel therapeutic strategies.
Purpose of the Study:
- To identify potential drug repurposing candidates for HNSCC using large-scale compound screening data.
- To uncover biomarkers associated with drug sensitivity and resistance in HNSCC.
Main Methods:
- Screening of 4,518 compounds across 28 HNSCC cell lines from the PRISM dataset.
- Integrative analysis of drug response and genomic data.
- Development of an RShiny web application for interactive data visualization.
Main Results:
- Identified 886 active compounds for HNSCC, including 418 targeted cancer drugs, 404 non-oncology drugs, and 64 chemotherapy agents.
- Shortlisted 36 compounds with significant killing activity for HNSCC repurposing.
- Confirmed association between EGFR ligand expression and osimertinib sensitivity.
- Discovered novel biomarkers for MEK inhibitor sensitivity (immune signaling) and resistance (cell cycle).
Conclusions:
- This study provides a valuable database of HNSCC drug sensitivity profiles for drug repurposing.
- Identified prioritized drug candidates and potential biomarkers for HNSCC treatment.
- The approach can inform drug repurposing strategies for other cancer types.
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