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Related Experiment Video

Updated: May 17, 2025

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Deciphering Nicotine-Driven Oncogenesis in Head and Neck Cancer: Integrative Transcriptomics and Drug Repurposing

Guo-Rung You1, Daniel Yu Chang1, Hung-Han Huang1,2

  • 1Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.

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|May 14, 2025
PubMed
Summary

Chronic nicotine exposure promotes head and neck cancer (HNC) by altering gene expression. Researchers identified potential drug therapies, AZD1332 and JAK-8517, for treating tobacco-associated HNC.

Keywords:
drug repurposinghead and neck cancer (HNC)nicotineoncogenic pathwaytranscriptomic analysis

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Chronic nicotine exposure is a known driver of head and neck cancer (HNC) progression.
  • The precise molecular mechanisms underlying nicotine's role in HNC remain incompletely understood.
  • Investigating these mechanisms is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To elucidate the transcriptomic alterations induced by chronic nicotine exposure in HNC.
  • To identify potential therapeutic targets and repurposable drugs for tobacco-associated HNC.
  • To characterize the molecular landscape of nicotine-driven HNC.

Main Methods:

  • Head and neck cancer cell lines were chronically exposed to nicotine to mimic habitual smoking.
  • Transcriptomic profiling was performed and integrated with The Cancer Genome Atlas (TCGA) HNSC data.
  • Functional pathway enrichment analysis and drug repurposing via gene-drug correlation analysis were conducted.

Main Results:

  • A set of 168 genes (Nic-HNC gene set) was identified, comprising 149 oncogenes and 19 tumor suppressors.
  • Nicotine exposure upregulated oncogenic signaling pathways (e.g., PI3K-AKT) and suppressed immune regulation.
  • Five potential therapeutic compounds were identified, with AZD1332 and JAK-8517 showing promise against nicotine-induced oncogenes.

Conclusions:

  • This study provides a comprehensive molecular characterization of nicotine-induced HNC.
  • AZD1332 and JAK-8517 are proposed as promising drug candidates for targeted therapy in tobacco-associated HNC.
  • The findings lay the groundwork for translational research into novel HNC interventions.