Related Experiment Video
Updated: May 17, 2025

Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
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.
Abstract:
Background: Chronic nicotine exposure drives head and neck cancer (HNC) progression, yet its molecular mechanisms remain underexplored. This study examines nicotine-induced transcriptomic changes and potential therapies via drug repurposing. Methods: HNC cell lines (OECM1, SAS, and CGHNC9) were exposed to an IC30 nicotine dose for three months to model chronic exposure in habitual smokers. Transcriptomic profiling of these sublines was integrated with TCGA-HNSC patient data. Differentially expressed genes (DEGs) underwent functional pathway enrichment analysis. Drug repurposing was conducted using gene-drug correlation analysis across GDSC, CTRP, and PRISM databases. Results: Transcriptomic analysis identified 1223 DEGs in nicotine-exposed HNC cells, and integration with TCGA-HNSC data defined a Nic-HNC gene set of 168 genes: 149 oncogenes and 19 tumor suppressors, with 36 oncogenes overexpressed in heavy smokers. Pathway analysis revealed the upregulation of oncogenic signaling, such as PI3K-AKT, alongside the suppression of immune regulation and metabolic reprogramming. Drug repurposing identified five compounds-AZD1332, JAK-8517, NU7441, BRD-K30748066, and neopeltolide-with the first two exhibiting the strongest inverse correlations with nicotine-induced oncogenes in heavy smokers, highlighting their potential as targeted therapies for tobacco-associated HNC. Conclusions: This study comprehensively characterizes nicotine-driven molecular dysregulation in HNC and proposes AZD1332 and JAK-8517 as promising therapeutic candidates through drug repurposing. These insights advance our understanding of nicotine's oncogenic role and provide a foundation for translational research to develop targeted interventions for tobacco-associated HNC.
Insights
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.
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.
More Related Videos
Related Concept Videos
Targeted Cancer Therapies
There are several types of targeted therapies against...
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
Mutagenicity and Carcinogenicity
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Mechanisms of Retrovirus-induced Cancers

