Organoid drug screening (PDTO mini-ring platform)
Overview
Patient-derived tumor organoid (PDTO) drug screening is a functional precision medicine approach in which primary tumor cells are cultured as 3D organoids in a miniaturized 96-well “mini-ring” format and exposed to large compound libraries. Viability is measured by CellTiter-Glo at day 5; results are returned within one week of surgery, enabling rapid pre-treatment drug sensitivity profiling.
Used by
- PMID:39305899 — A UCLA sarcoma biobank of 194 specimens from 126 patients (24 bone and soft-tissue subtypes) generated PDTOs with ~93% take rate; 92 specimens screened against ≥10 of >400 single agents and combinations (mean 117 drugs/sample). At least one FDA-approved or NCCN-recommended effective regimen was identified for 59% of specimens (57/97) and 58% of patients (43/74). Organoid responses to MAP chemotherapy correlated with post-resection necrosis and PFS in three osteosarcoma cases. The PREMOST trial (NCT06064682) was motivated by these findings PMID:39305899.
- Used to test enzalutamide, everolimus, and BKM-120 (buparlisib) in seven patient-derived prostate cancer organoid lines; AR-amplified MSK-PCa2 was exquisitely sensitive to enzalutamide (IC50 ~50 nM) while other lines were resistant. PMID:25201530
Notes
- Z’ or robust-Z’ ≥ 0.2 required for plate-quality inclusion; top-5% viability score used to define a “significant response.”
- Intra-patient heterogeneity was prominent (e.g., Pearson correlations 0.64–0.84 across three same-surgery metastases in one epithelioid sarcoma patient); single-sample recommendations may not represent disseminated disease.
- 43% of identified active compounds are pre-clinical or terminated; only 5% are NCCN-preferred for the matched indication — drug access and approval pathways are a major adoption barrier.
- Corpus-grown slug; not present in canonical ontology.
Sources
This page was processed by entity-page-writer on 2026-05-01. - PMID:25201530
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