Related Experiment Video
Updated: Jul 2, 2025
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Unveiling Epigenetic Vulnerabilities in Triple-Negative Breast Cancer through 3D Organoid Drug Screening
Xinxin Rao1,2,3, Zhibin Qiao1,2,3, Yang Yang1,2,3
1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Abstract:
Triple-negative breast cancer (TNBC) poses a therapeutic challenge due to its aggressive nature and lack of targeted therapies. Epigenetic modifications contribute to TNBC tumorigenesis and drug resistance, offering potential therapeutic targets. Recent advancements in three-dimensional (3D) organoid cultures, enabling precise drug screening, hold immense promise for identifying novel compounds targeting TNBC. In this study, we established two patient-derived TNBC organoids and implemented a high-throughput drug screening system using these organoids and two TNBC cell lines. Screening a library of 169 epigenetic compounds, we found that organoid-based systems offer remarkable precision in drug response assessment compared to cell-based models. The top 30 compounds showing the highest drug sensitivity in the initial screening were further assessed in a secondary screen. Four compounds, panobinostat, pacritinib, TAK-901, and JIB-04, targeting histone deacetylase, JAK/STAT, histone demethylases, and aurora kinase pathways, respectively, exhibited potent anti-tumor activity in TNBC organoids, surpassing the effect of paclitaxel. Our study highlights the potential of these novel epigenetic drugs as effective therapeutic agents for TNBC and demonstrates the valuable role of patient-derived organoids in advancing drug discovery.
Insights
Patient-derived triple-negative breast cancer (TNBC) organoids precisely screened epigenetic drugs. Four compounds showed potent anti-tumor activity, offering new therapeutic options for TNBC.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
- Epigenetic alterations are implicated in TNBC development and treatment resistance.
- Patient-derived organoids offer a promising platform for personalized drug screening.
Purpose of the Study:
- To identify novel epigenetic compounds with anti-tumor activity against TNBC.
- To evaluate the precision of 3D organoid models for high-throughput drug screening.
- To compare the efficacy of identified compounds with standard chemotherapy.
Main Methods:
- Establishment of two patient-derived TNBC organoid models.
- High-throughput screening of 169 epigenetic compounds using organoids and cell lines.
- Secondary screening of top-performing compounds for anti-tumor efficacy.
Main Results:
- Organoid-based drug screening demonstrated higher precision in response assessment than cell-based models.
- Four epigenetic compounds (panobinostat, pacritinib, TAK-901, JIB-04) exhibited significant anti-tumor activity.
- These compounds targeted histone deacetylase, JAK/STAT, histone demethylase, and aurora kinase pathways.
Conclusions:
- Patient-derived TNBC organoids are valuable tools for advancing drug discovery.
- Novel epigenetic drugs show potential as effective therapeutic agents for TNBC.
- Targeting epigenetic pathways offers a promising strategy for TNBC treatment.
