Related Experiment Video
Updated: Apr 8, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Evaluation of Epigenetic Drug Targeting of Heterogenous Tumor Cell Fractions Using Potential Biomarkers of Response
Anand Kamal Singh1, Nishi Chandra1, Sharmila A Bapat2
1National Centre for Cell Science, NCCS Complex, Pune, Maharashtra, India.
Purpose:
Resolution of aberrant epigenetic changes leading to altered gene expression during transformation and tumor progression is pertinent for mechanistic understanding of disrupted pathways in cancer. Such changes provide for biomarkers that can be applied in drug screening and improved disease management.
Experimental Design:
Genome-wide profiling and analyses of promoter DNA methylation, histone modifications, and gene expression of an in vitro progression model of serous ovarian adenocarcinoma were carried out. Similar in silico analyses and comparison of methylation and gene expression of early- and late-grade ovarian cancer samples in The Cancer Genome Atlas assigned a clinical relevance to our study. Candidate biomarkers were evaluated for epigenetic drug treatments in experimental animal models on a background of differing tumor cell responses arising from intratumor heterogeneity.
Results:
Differentially regulated genes during tumor progression were identified through the previously mentioned analyses as candidate biomarkers. In examining the tumor suppressor PTGIS as a potential biomarker for treatment with either 5-Aza-dC or TSA, 5-Aza-dC effectively stabilized cell cycling, restricted genetic instability, and derepressed PTGIS expression, while TSA led to emergence of drug-resistant progenitors lacking PTGIS expression. Profiling MEST and RXRγ for curcumin and CBB1007, respectively, indicated an inability of curcumin and CBB1007 in restricting residual tumor regenerative capabilities.
Conclusions:
Our study provides novel insights into epigenetic regulation in ovarian cancer progression and potential biomarkers for evaluating efficacy of epigenetic drugs in restricting residual tumor regeneration. Such approaches may assign a new functional interpretation of drug efficacy and cell tumor responses in ovarian cancer.
Insights
This study identifies epigenetic biomarkers for ovarian cancer progression. Certain epigenetic drugs show promise in stabilizing cell cycling and restricting tumor growth, while others may lead to drug resistance.
Area of Science:
- Oncology
- Epigenetics
- Cancer Biology
Background:
- Aberrant epigenetic changes drive altered gene expression during cancer development.
- Understanding these changes is crucial for identifying cancer biomarkers and improving treatment strategies.
Purpose of the Study:
- To investigate epigenetic alterations in ovarian cancer progression.
- To identify potential biomarkers for drug screening and disease management.
- To evaluate the efficacy of epigenetic drugs in preclinical models.
Main Methods:
- Genome-wide profiling of DNA methylation, histone modifications, and gene expression in an ovarian cancer model.
- In silico analysis and comparison with The Cancer Genome Atlas data.
- Evaluation of candidate biomarkers and epigenetic drug treatments in experimental animal models.
Main Results:
- Identified differentially regulated genes as candidate biomarkers for ovarian cancer progression.
- 5-Aza-dC stabilized cell cycling and derepressed PTGIS, a tumor suppressor, while TSA induced drug-resistant progenitors.
- Curcumin and CBB1007 showed limited efficacy in restricting residual tumor regenerative capabilities.
Conclusions:
- Novel insights into epigenetic regulation in ovarian cancer progression.
- Identified potential biomarkers for evaluating epigenetic drug efficacy.
- Suggests new interpretations for drug efficacy and cellular responses in ovarian cancer treatment.
