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GARD: Genomic Data based Drug Repurposing in Head and Neck Cancer with Large Language Model Validation.

Pradham Tanikella1, Will Nenad2, Christophe Courtine3

  • 1Department of Genetics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina.

Biorxiv : the Preprint Server for Biology
|February 6, 2026
PubMed
Summary
This summary is machine-generated.

The GARD pipeline identifies new drug repurposing candidates for head and neck cancer (HNC) by integrating genomic data and network analysis. This approach accelerates the discovery of personalized treatments, offering cost-effective therapeutic options.

Keywords:
Drug repurposingGenomicsHead and Neck Cancer

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Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Head and neck cancer (HNC) is a globally prevalent malignancy with limited treatment outcome improvements.
  • Drug repurposing offers a cost-effective strategy to identify novel therapeutic options using existing drugs with known safety profiles.

Purpose of the Study:

  • To develop and implement the GARD (Genomic Alteration-based Repurposing for Drugs) pipeline for identifying drug repurposing candidates in HNC.
  • To leverage genomic and network-based approaches for uncovering precision medicine strategies in HNC.

Main Methods:

  • The GARD pipeline integrates multi-omics data (CNV, somatic mutations) from TCGA, stratified by HPV status.
  • Risk-associated genes were identified, expanded via protein-protein interaction (PPI) networks, and literature-validated using LLM analysis of PubMed.
  • Validated genes and network neighbors were mapped against DrugBank to identify significant drug-gene associations.

Main Results:

  • Identified significant HNC-associated genes (e.g., PIK3CA, SOX2, TP53) across HPV+ and HPV- subgroups.
  • Network expansion identified additional targetable genes (e.g., EGFR, ERBB2, FGFRs).
  • Drug-gene mapping revealed candidates in clinical trials and novel repurposing agents (e.g., Afatinib, Cabozantinib, Amuvatinib, Quercetin, Aspirin).

Conclusions:

  • The GARD pipeline provides a genomics-driven, network-informed framework for systematic drug repurposing in HNC.
  • HPV stratification, literature validation, and integrated drug mapping enhance precision and accelerate the discovery of personalized HNC treatments.