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Updated: Sep 27, 2025
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Published on: February 7, 2021
Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants
Margaret M Centenera1,2,3, Andrew D Vincent1,2, Max Moldovan4
1Adelaide Medical School, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia.
Abstract:
Prostate cancer is a complex and heterogeneous disease, but a small number of cell lines have dominated basic prostate cancer research, representing a major obstacle in the field of drug and biomarker discovery. A growing lack of confidence in cell lines has seen a shift toward more sophisticated pre-clinical cancer models that incorporate patient-derived tumors as xenografts or explants, to more accurately reflect clinical disease. Not only do these models retain critical features of the original tumor, and account for the molecular diversity and cellular heterogeneity of prostate cancer, but they provide a unique opportunity to conduct research in matched tumor samples. The challenge that accompanies these complex tissue models is increased complexity of analysis. With over 10 years of experience working with patient-derived explants (PDEs) of prostate cancer, this study provides guidance on the PDE method, its limitations, and considerations for addressing the heterogeneity of prostate cancer PDEs that are based on statistical modeling. Using inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) as an example of a drug that induces robust proliferative response, we demonstrate how multi-omics analysis in prostate cancer PDEs is both feasible and essential for identification of key biological pathways, with significant potential for novel drug target and biomarker discovery.
Insights
Patient-derived explants (PDEs) offer a more accurate model for prostate cancer research than traditional cell lines. Multi-omics analysis of prostate cancer PDEs is essential for discovering new drug targets and biomarkers.
Area of Science:
- Oncology
- Translational Research
- Genomics
Background:
- Prostate cancer research is hindered by reliance on limited cell lines that do not reflect disease complexity.
- Patient-derived explants (PDEs) are emerging as superior preclinical models, preserving tumor heterogeneity and molecular diversity.
- Analyzing matched tumor samples from PDEs offers unique research opportunities.
Purpose of the Study:
- To provide guidance on utilizing prostate cancer patient-derived explants (PDEs) for research.
- To address the analytical challenges associated with the heterogeneity of prostate cancer PDEs.
- To demonstrate the feasibility and importance of multi-omics analysis in PDEs for drug and biomarker discovery.
Main Methods:
- Utilized over 10 years of experience with prostate cancer patient-derived explants (PDEs).
- Developed statistical modeling approaches to manage prostate cancer PDE heterogeneity.
- Applied multi-omics analysis to PDEs treated with heat shock protein 90 (Hsp90) inhibitors.
Main Results:
- Prostate cancer PDEs accurately reflect clinical disease, retaining critical tumor features and molecular diversity.
- Multi-omics analysis in prostate cancer PDEs is feasible and essential for identifying key biological pathways.
- Hsp90 inhibitors demonstrated a robust proliferative response in PDE models.
Conclusions:
- Patient-derived explants (PDEs) represent a significant advancement over traditional cell lines for prostate cancer research.
- Multi-omics analysis of prostate cancer PDEs is crucial for uncovering novel drug targets and biomarkers.
- This study provides a framework for leveraging PDEs to overcome limitations in prostate cancer drug and biomarker discovery.
