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Updated: Nov 24, 2025
Establishment and Culture of Patient-Derived Breast Organoids
Published on: February 17, 2023
Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment
Elena Campaner1,2, Alessandro Zannini1,2, Mariangela Santorsola1,2
1Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
Abstract:
Tumor organoids are tridimensional cell culture systems that are generated in vitro from surgically resected patients' tumors. They can be propagated in culture maintaining several features of the tumor of origin, including cellular and genetic heterogeneity, thus representing a promising tool for precision cancer medicine. Here, we established patient-derived tumor organoids (PDOs) from different breast cancer subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple negative). The established model systems showed histological and genomic concordance with parental tumors. However, in PDOs, the ratio of diverse cell populations was frequently different from that originally observed in parental tumors. We showed that tumor organoids represent a valuable system to test the efficacy of standard therapeutic treatments and to identify drug resistant populations within tumors. We also report that inhibitors of mechanosignaling and of Yes-associated protein 1 (YAP) activation can restore chemosensitivity in drug resistant tumor organoids.
Insights
Patient-derived tumor organoids (PDOs) model breast cancer heterogeneity, aiding precision medicine. These organoids can identify drug resistance and show that YAP inhibitors restore chemosensitivity in resistant models.
Area of Science:
- Oncology
- Cancer Research
- Cell Biology
Background:
- Tumor organoids are 3D in vitro models derived from patient tumors.
- They maintain tumor heterogeneity, offering potential for precision cancer medicine.
Purpose of the Study:
- To establish and characterize patient-derived tumor organoids (PDOs) from diverse breast cancer subtypes.
- To evaluate PDOs as a model for testing therapeutic efficacy and identifying drug resistance.
- To investigate the role of mechanosignaling and YAP activation in drug resistance.
Main Methods:
- Establishing PDOs from surgically resected breast tumors across different subtypes.
- Histological and genomic analysis to confirm concordance with parental tumors.
- Testing standard therapeutic treatments and identifying drug-resistant populations within PDOs.
Main Results:
- PDOs from luminal A, luminal B, HER2-enriched, and triple-negative breast cancers were successfully established.
- Histological and genomic profiles of PDOs largely matched parental tumors, but cell population ratios differed.
- PDOs effectively predicted treatment efficacy and revealed drug-resistant subpopulations.
- Inhibitors of mechanosignaling and YAP activation resensitized drug-resistant PDOs to chemotherapy.
Conclusions:
- PDOs are valuable models for precision oncology, reflecting tumor heterogeneity.
- PDOs can identify drug resistance mechanisms and serve as platforms for drug screening.
- Targeting mechanosignaling and YAP pathways may overcome drug resistance in breast cancer.
