Method Profile
Select resistant triple-negative breast cancer (TNBC) organoids with a clinical-data-derived biomarker model, then screen combinations with cisplatin and validate by imaging and dose matrices.
Generate treatment hypotheses for a clinically defined platinum-resistant breast cancer state.
26 existing breast organoid transcriptomes plus 14 TNBC cultures for model characterization; TORG40 for the primary 386-compound screen.
Clinical veliparib/carboplatin response model; organoid cisplatin/veliparib testing; 386-compound screen with/without 5 μM cisplatin; secondary imaging and ABT-263 dose matrices.
Models and clinical data
HUB and TNBC TORG organoids; I-SPY2 biomarker/response dataset.
Measurements
RNA biomarkers, ATP viability, CellTox cell-death imaging, bright-field morphology and Bliss synergy analysis.
Candidate-alone and cisplatin-backbone responses are compared with matched controls and secondary imaging. The clinical biomarker model used carboplatin, while the culture experiments used cisplatin.
Test clinical-biomarker predictions in organoids, then compare selected cisplatin combinations.
14 TNBC cultures characterized; detailed VP response in 4; primary screen in TORG40; ABT-263 synergy in TORG40/TORG58/TORG139.
Predicted response groups; cisplatin/veliparib monotherapies and combination; candidate drug with versus without cisplatin.
Organoid responses were broadly concordant with predictions. ABT-263/cisplatin mean Bliss scores 11.02–31.57 supported synergy in tested matrices.
A study links I-SPY2 response biomarkers to breast cancer organoid models, then screens resistant cultures for cisplatin combinations. BCL-2 family findings remain preclinical; exploratory HSP90 follow-up found no significant pathological-response improvement in a clinical subgroup.
