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Updated: Mar 11, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
PPARγ targeted oral cancer treatment and additional utility of genomics analytic techniques
Nathan Handley1, Jacob Eide1, Randall Taylor2
1Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, U.S.A.
Objective:
Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to have anti-proliferative, anti-angiogenic, and proapoptotic effects, leading to interest in their use as cancer therapeutics. Pioglitazone, a U.S. Food and Drug Administration-approved type II diabetes medication and PPARγ agonist, may have a role in adjuvant head-and-neck squamous cell carcinoma treatment or prevention. Therefore, the purpose of this study was: 1) to treat oral cavity cancer cells with the PPARγ activator, pioglitazone, to analyze gene expression changes; and 2) to compare those changes with our preexisting genomic data for development of hypothesis-driven additional basic and clinical studies.
Study Design:
Prospective in vitro.
Methods:
We utilized microarray technology, as well as OCPlus (Bioconductor open source software) and Ingenuity Pathway Analysis (Qiagen, Redwood City, CA), to analyze differential gene expression in tumor and pioglitazone-treated tumor cells on a genome-wide level to demonstrate the feasibility of such an approach and determine appropriate sample size for future investigations.
Results:
We found that approximately 35 samples are required to adequately power future studies. We next discovered that pioglitazone significantly affects Inducible T-Cell Costimulator (iCOS)-Ligand for the T-cell-specific cell surface receptor ICOS (iCOSL) and type II diabetes mellitus pathways as a putative anti-cancer mechanism.
Conclusion:
Genome-wide analysis is possible for the exploration of differential pathway modulation and rapid hypothesis generation. Both inflammation and type II diabetes pathways were significantly altered and therefore might provide unique hypothesis-driven pharmacodynamic parameters for future in vitro or in vivo studies utilizing thiazolidinediones. These techniques could be applied to microarray or other high throughput data from a variety of hypothesis-generating research scenarios in otolaryngology (e.g., middle ear proteomics, sinus microbiome studies).
Level Of Evidence:
NA. Laryngoscope, 127:E124-E131, 2017.
Insights
Pioglitazone, a diabetes drug, shows potential as an anti-cancer agent by altering gene expression in oral cancer cells. Further research is needed to confirm its efficacy in head-and-neck squamous cell carcinoma treatment.
Area of Science:
- Oncology
- Pharmacology
- Genomics
Background:
- Peroxisome proliferator-activated receptor γ (PPARγ) agonists exhibit anti-cancer properties.
- Pioglitazone, a PPARγ agonist and type II diabetes medication, is being investigated for its potential in head-and-neck squamous cell carcinoma (HNSCC).
Purpose of the Study:
- To investigate the effects of pioglitazone on gene expression in oral cavity cancer cells.
- To compare observed gene expression changes with existing genomic data for future research hypotheses.
Main Methods:
- Prospective in vitro study design.
- Microarray technology and bioinformatics tools (OCPlus, Ingenuity Pathway Analysis) were used for genome-wide differential gene expression analysis.
- Determined sample size for future studies.
Main Results:
- Approximately 35 samples are required for adequate statistical power in future investigations.
- Pioglitazone significantly impacts Inducible T-Cell Costimulator Ligand (iCOSL) and type II diabetes mellitus pathways.
- Identified potential anti-cancer mechanisms linked to these pathways.
Conclusions:
- Genome-wide analysis facilitates pathway modulation exploration and hypothesis generation.
- Inflammation and type II diabetes pathways are significantly altered, offering pharmacodynamic parameters for future thiazolidinedione studies.
- The methodology is applicable to various hypothesis-generating research in otolaryngology.
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