Method Profile
Compare chemotherapy responses in gastric organoids with and without signet-ring cell carcinoma components.
Subtype-associated pharmacology and exploratory matching to clinical chemotherapy outcomes.
17 gastric cancer organoid cultures were established from 27 tissue samples: 5 with 20–60% signet-ring components and 12 without. Drug comparisons used 13 models, comprising 4 with signet-ring components and 9 without.
Four-day organoid growth followed by 4–6 days of drug exposure and MTS measurement. Five single agents were compared.
Drugs
5-fluorouracil, oxaliplatin, SN38, paclitaxel and epirubicin; 0.1% DMSO vehicle.
Model characterization
Histology and whole-exome mutation/copy-number comparisons with parental tumors.
Compare inhibition at the source-defined plasma-reference concentrations and full dose-response profiles, then examine associations with the clinical regimen received.
SRCC-component versus non-SRCC organoid comparison with a small observational clinical follow-up.
Drug-tested population: 13 models, 4 with signet-ring components and 9 without, from the 17 established cultures. The clinical heatmap contains 13 cases; Fig5A adjuvant survival groups are 6 sensitive and 4 resistant, while Fig5B stage IV groups are 1 and 2.
Vehicle; five drug classes; non-SRCC models; matched clinical outcomes.
Models with signet-ring components were less sensitive to 5-fluorouracil and oxaliplatin than the other models (P = 0.011 and 0.003). Between-subtype differences for SN38, paclitaxel and epirubicin were not significant.
Thirteen drug-tested gastric cancer organoids revealed subtype-associated chemotherapy differences. Four models with signet-ring components were less sensitive to fluorouracil and oxaliplatin than nine non-signet-ring models; differences for three other drugs did not reach significance.
