Summary
This proof-of-principle study describes the development and characterisation of a novel patient-derived xenograft model (PNPCa) derived from treatment-naïve prostate cancer soft tissue metastasis, harbouring rare BRCA2 and CHD1 somatic mutations with microsatellite instability—a genomic profile present in approximately 3% of advanced prostate cancer cases and previously unmodelled in vivo. Comparative medium-throughput organoid screening of FDA-approved compounds across treatment-naïve and metastatic PDX models revealed differential drug sensitivities, with multikinase inhibitors (ponatinib, sunitinib, sorafenib) demonstrating broad efficacy against organoids from advanced, treatment-resistant cases. The work provides a preclinical tool potentially useful for screening drug responses to both standard-of-care and repurposed compounds in prostate cancer.
UK applicability
This laboratory-based preclinical model development study is not directly applicable to UK farming systems, soil health, or food production. Its relevance to Vitagri's Pulse Brain catalogue on agricultural systems and nutrition is not evident from the content.
Key measures
Transcriptomic and genomic profiling (RNA sequencing, whole-exome sequencing); drug sensitivity screening of FDA-approved compounds; identification of multikinase inhibitor efficacy
Outcomes reported
The study developed and characterised patient-derived xenograft (PDX) and organoid models of prostate cancer harbouring BRCA2, CHD1 mutations and microsatellite instability, and screened FDA-approved compounds to identify differential drug sensitivities across treatment-naïve and metastatic PDX models.
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