Related Experiment Video
Updated: Apr 18, 2026
09:01
Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies
Published on: July 3, 2025
1.1K
Integrative Transcriptomic and Machine Learning Analysis of ecDNA-Associated Features for Studying Chemotherapy
Md Iftehimul1, Dipongkor Saha2
1Institute of Biotechnology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh.
Biorxiv : the Preprint Server for Biology
|April 17, 2026
Summary
Extrachromosomal DNA (ecDNA) contributes to cancer drug resistance by altering gene expression and accumulating mutations over time. Understanding ecDNA dynamics can predict and potentially overcome chemotherapy resistance in aggressive cancers.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Extrachromosomal DNA (ecDNA) drives oncogene amplification in aggressive cancers.
- The role of ecDNA in chemotherapy resistance in vivo is not fully understood.
Purpose of the Study:
- Investigate ecDNA's contribution to chemotherapy resistance in triple-negative breast cancer (TNBC).
- Identify ecDNA-associated molecular features predictive of therapeutic resistance.
Main Methods:
- Analyzed RNA-seq data from 4T1 TNBC cells and tumors at various growth stages.
- Used molecular docking to predict ecDNA-protein-drug interactions.
- Employed machine learning models to predict ecDNA-associated drug resistance.
Main Results:
- Observed temporal changes in gene expression and ecDNA alterations over tumor growth.
- Detected gradual accumulation of mutations in ecDNA genes, potentially reducing drug binding.
- Machine learning models identified ecDNA burden and prevalence as key predictors of resistance.
- Paclitaxel and doxorubicin showed higher resistance probabilities, while hydroxyurea showed reduced resistance.
Conclusions:
- ecDNA undergoes temporal remodeling in TNBC, influencing chemoresistance.
- ecDNA burden and mutations are significant predictive features for drug resistance.
- Targeting ecDNA may offer novel therapeutic strategies for TNBC.
