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.

Cancers
|May 14, 2025
PubMed

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.

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.4K
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
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...
7.5K
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.2K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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...
4.8K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.0K