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Updated: Oct 18, 2025
Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
Published on: October 24, 2019
Patient derived organoids in prostate cancer: improving therapeutic efficacy in precision medicine
Sahithi Pamarthy1, Hatem E Sabaawy2,3,4,5
1Rutgers Cancer Institute of New Jersey, Rutgers University, 195 Little Albany St, Rm 4557, New Brunswick, NJ, 08901, USA.
Abstract:
With advances in the discovery of the clinical and molecular landscapes of prostate cancer (PCa), implementation of precision medicine-guided therapeutic testing in the clinic has become a priority. Patient derived organoids (PDOs) are three-dimensional (3D) tissue cultures that promise to enable the validation of preclinical drug testing in precision medicine and coclinical trials by modeling PCa for predicting therapeutic responses with a reliable efficacy. We evaluate the advances in 3D culture and PDO use to model clonal heterogeneity and screen for effective targeted therapies, with a focus on the technological advances in generating PDOs. Recent innovations include the utilization of PDOs both in original research and/or correlative studies in clinical trials to examine drug effects within the PCa tumor microenvironment (TME). There has also been a significant improvement with the utilization of various extracellular matrices and single cell assays for the generation and long-term propagation of PDOs. Single cell derived PDOs could faithfully recapitulate the original tumor and reflect the heterogeneity features. While most PDO use for precision medicine understandably involved tissues derived from metastatic patients, we envision that the generation of PDOs from localized PCa along with the incorporation of cells of the TME in tissue models would fulfill the great potential of PDOs in predicting drug clinical benefits. We conclude that single cell derived PDOs reiterate the molecular features of the original tumor and represent a reliable pre-clinical PCa model to understand individual tumors and design tailored targeted therapies.
Insights
Patient-derived organoids (PDOs) are advancing prostate cancer (PCa) research. These 3D models accurately reflect tumor features, aiding in predicting treatment responses and developing targeted therapies.
Area of Science:
- Oncology
- Precision Medicine
- 3D Tissue Engineering
Background:
- Advances in understanding prostate cancer (PCa) molecular and clinical features necessitate precision medicine approaches.
- Patient-derived organoids (PDOs) are emerging as powerful tools for preclinical drug testing and clinical trial validation in PCa.
Purpose of the Study:
- To review technological advancements in generating PDOs for modeling PCa.
- To highlight the utility of PDOs in predicting therapeutic responses and understanding the tumor microenvironment (TME).
Main Methods:
- Evaluation of 3D culture techniques and PDO generation, focusing on innovations in extracellular matrices and single-cell assays.
- Assessment of PDOs' ability to model clonal heterogeneity and recapitulate original tumor molecular features.
- Review of PDO applications in preclinical research and correlative studies within clinical trials.
Main Results:
- Single-cell derived PDOs can faithfully recapitulate original tumor heterogeneity and molecular profiles.
- Innovations in PDO generation, including extracellular matrices and single-cell assays, have improved their utility.
- PDOs are increasingly used to study drug effects within the PCa tumor microenvironment.
Conclusions:
- Single-cell derived PDOs are reliable preclinical models for understanding individual PCa tumors.
- PDOs hold significant potential for designing tailored targeted therapies and predicting clinical drug benefits.
- Future directions include generating PDOs from localized PCa and incorporating TME cells for enhanced predictive power.
