Anne B. Richardson, Payel Chatterjee, Rachele Rosati, Alex Rajewski, Robert L. Diaz, Lauren Appleyard, Shalini Pereira, Brady Bernard, Milind Javle, Gentry Teng King, Adam Diehl, William Proctor Harris, Sameek Roychowdhury, Christopher J. Kemp, Carla Grandori
Abstract Biliary tract cancers (BTCs) pose clinical challenges due to poor chemotherapy response and aggressive disease course. We evaluated patient derived tumor organoid (PDTO) based drug sensitivity testing as a tool to guide therapy. In this multicenter study, 26 tumor organoids were successfully derived from 43 BTC patients and tested with an average of 50 cancer-directed therapies using the CLIA certified PARIS® assay. Despite most organoids being from late-stage disease, 24/26 (92.3%) exhibited strong sensitivity to one or more targeted agents. Active drugs included inhibitors of EGFR/HER2, MEK, ERK, BCR-ABL and SRC family, mTOR, PI3K, MDM2, BCL2, and BET. Drug sensitivities aligned with known genetic biomarkers, but were also observed in cultures lacking them, indicating ex vivo testing can expand actionability beyond genomics. In five cases, results guided therapy; one patient with an FGFR-BICC1 fusion refractory to FGFR inhibitors responded to dasatinib, achieving symptomatic improvement, stable disease, and >8 month survival.