Related Experiment Video
Updated: Jun 8, 2025
Establishment and Culture of Patient-Derived Breast Organoids
Published on: February 17, 2023
Patient-Derived Organoids on a Microarray for Drug Resistance Study in Breast Cancer
Tianyuan Fang1, Xinlun Xie1, Wei Lu2
1Department of Chemistry, Zhejiang University, Hangzhou 310058, China.
Abstract:
Drug resistance is always a challenge in cancer treatment, whether for chemotherapy, targeting, or immunotherapy. Although tumor cell lines are derived from cancer patients, they gradually lost the original characteristics, including heterogeneity and tumor microenvironment (TME), during the long period of in vitro culturing. Therefore, it is urgent to use patient-derived tumor models instead of cancer cell lines to study tumor drug resistance. Herein, we developed a microarray device that serves as a platform for high-throughput and three-dimensional culture of breast cancer patient-derived organoids (BCOs) and investigated their resistance to adriamycin (ADM). Coupled with fluorescence microscopy, this system enabled on-chip drug response monitoring and cell viability assessment without the consumption of a large number of tumor cells. The organoids were divided into a resistant BCO group (RBCO) and a sensitive BCO group (SBCO) according to their half-inhibitory concentration (IC50). Different from cancer cell lines, BCOs demonstrated obvious heterogeneity in drug treatment. Ivermectin (IVM), a broad-spectrum antiparasitic agent approved by the Food and Drug Administration (FDA), was observed to synergistically augment ADM-induced cytotoxicity in organoids. The BCO chip provides a promising platform for investigation of drug resistance and preclinical drug screening based on clinical samples.
Insights
Patient-derived organoids cultured on a microarray chip effectively model breast cancer drug resistance. This platform identified ivermectin as a potential synergistic agent to enhance adriamycin treatment efficacy.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- Drug resistance remains a significant hurdle in cancer therapy across various treatment modalities.
- Traditional cancer cell lines often fail to replicate patient tumor heterogeneity and the tumor microenvironment (TME).
- Patient-derived tumor models are crucial for accurately studying drug resistance mechanisms.
Purpose of the Study:
- To develop a microarray device for high-throughput, 3D culture of breast cancer patient-derived organoids (BCOs).
- To investigate BCO resistance to adriamycin (ADM) and assess drug response using on-chip monitoring.
- To explore the potential of ivermectin (IVM) in overcoming ADM resistance.
Main Methods:
- Development of a microarray device for 3D culturing of BCOs.
- On-chip drug response monitoring and cell viability assessment using fluorescence microscopy.
- Classification of BCOs into resistant (RBCO) and sensitive (SBCO) groups based on IC50 values.
Main Results:
- BCOs exhibited significant heterogeneity in response to ADM treatment, unlike cancer cell lines.
- The developed BCO chip enabled efficient drug response monitoring with minimal cell consumption.
- Ivermectin demonstrated a synergistic effect, augmenting ADM-induced cytotoxicity in resistant BCOs.
Conclusions:
- The BCO chip is a promising platform for studying drug resistance in patient-derived breast cancer models.
- This system facilitates preclinical drug screening using clinical samples.
- The findings suggest a potential therapeutic strategy combining ADM and IVM for resistant breast cancers.
