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Updated: Jun 28, 2026
Establishment of Pancreatic Cancer-Derived Tumor Organoids and Fibroblasts From Fresh Tissue
Published on: May 26, 2023
Patient-derived organoids across cancers reveal conserved tumor heterogeneity and actionable therapeutic
Hui-Hsuan Kuo1, Bhavneet Bhinder1,2, Hamza N Gokozan3
1Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Abstract:
We developed a pan-cancer patient-derived organoid (PDO) platform comprising 220 PDOs from 191 patients across 15 cancer types to advance functional precision oncology. Comprehensive characterization demonstrated high fidelity to parent tumors, with 93% histopathology concordance, 80% median genomic concordance for driver mutations, and a 0.85 median gene expression correlation. Expression profiles remained largely stable over 10 passages, ensuring reproducibility for long-term screening. Clonality analysis showed that 85% of dominant tumor clones were preserved, with genomic concordance directly reflecting clonal similarity. Even PDOs with lower concordance retained key oncogenic drivers, validating their utility as disease models. Functional assays revealed that 58% of PDOs from patients ineligible for US Food and Drug Administration-approved poly(adenosine 5'-diphosphate-ribose) polymerase inhibitors were sensitive to talazoparib, linked to DNA damage repair alterations. Furthermore, combination screens identified agents that overcome resistance, particularly in TP53-mutant models. Our platform enables the investigation of targeted therapies and molecular drivers of drug sensitivity, providing translational insights for personalized treatment beyond current biomarker guidelines.
Insights
A new pan-cancer patient-derived organoid (PDO) platform accurately models tumors for drug screening. This functional precision oncology approach identifies novel targeted therapies and predicts drug sensitivity, advancing personalized cancer treatment.
Area of Science:
- Oncology
- Genomics
- Drug Discovery
Background:
- Patient-derived organoids (PDOs) are valuable models for cancer research.
- A need exists for robust, high-fidelity PDO platforms for comprehensive drug screening.
- Functional precision oncology requires reliable models that reflect tumor heterogeneity and genomic alterations.
Purpose of the Study:
- To develop and characterize a large-scale, pan-cancer patient-derived organoid platform.
- To assess the fidelity of PDOs to parent tumors at histopathological, genomic, and transcriptomic levels.
- To evaluate the utility of the PDO platform for drug sensitivity testing and identifying novel therapeutic strategies.
Main Methods:
- Development of a platform comprising 220 PDOs from 191 patients across 15 cancer types.
- Comprehensive characterization including histopathology, genomic sequencing, and gene expression profiling.
- Functional drug screening assays, including sensitivity testing to talazoparib and combination screens.
Main Results:
- High fidelity of PDOs to parent tumors: 93% histopathology concordance, 80% median genomic concordance, 0.85 median gene expression correlation.
- Stable expression profiles over 10 passages and preservation of dominant tumor clones (85%).
- Identification of talazoparib sensitivity in 58% of eligible PDOs and discovery of agents overcoming resistance in TP53-mutant models.
Conclusions:
- The established pan-cancer PDO platform offers high fidelity and reproducibility for functional precision oncology.
- The platform facilitates the investigation of targeted therapies and drug resistance mechanisms.
- This model provides translational insights for personalized cancer treatment beyond current biomarker guidelines.
