Study the consequences of metastatic sampling and tumor phenotype for functional drug profiling.
Model & Design
213 organoids from colorectal liver metastases in 102 patients; multiple spatial lesions were represented for 65 patients.
Experimental Format
96-hour ATP-associated viability screens in two drug libraries, with matched molecular and histological characterization.
Model Components
Component
Models
Description
Microsatellite-stable colorectal liver-metastasis organoids from a surgically treated cohort.
Component
Drug libraries
Description
41- and 47-drug libraries with 24 shared drugs for principal cross-library comparisons.
Component
Context
Description
Morphology, mutations, gene expression and available radiological treatment histories.
Measurements & Endpoints
Drug sensitivity scores
Pairwise within-patient and between-patient response distances
Morphological and molecular correlates
Analysis
Harmonize common drug ranges, compare model pairs at their stated sampling time and preserve the separation of lesion and patient denominators.
Published Evidence
Study Design
Biobank-scale multi-lesion pharmacology and two selected treatment examples.
Study Sample
213 models from 102 patients; two prospective treatment decisions were described.
Comparison
Metastases within one patient versus models from different patients; cystic versus solid phenotypes.
Finding
Within-patient variation was lower overall but substantial in some patients; chemotherapy rechallenge and targeted therapy had different clinical outcomes.
Interpretation & Limits
Culture success was associated with poorer prognosis and weaker preceding treatment response.
Established-model sensitivity did not reproduce the lesions’ preceding neoadjuvant response.
Two treatment examples do not establish cohort-wide predictive accuracy.
A collection of 213 organoids from 102 patients compared liver metastases, molecular features and drug response. In two selected clinical cases, chemotherapy rechallenge produced a response, while metastases progressed during the targeted treatment.