Extended Data Fig. 11: A high-throughput tumouroid assay pipeline identifies anti-cancer drugs for repurposing as potential HCC therapy.
From: Human-correlated genetic models identify precision therapy for liver cancer
(a) Volumetric measurements of HCCOs after 9 d treatment with indicated drugs; merged data from 4 technical replicates in each of two plates per condition. Ranking position in parenthesis. Nucleobase/Nucleoside analogues indicated by asterisks. Box centre=median with box bounding 25–75th centiles, the upper whisker extend +/− 1.5*IQR from the hinge. N = 2421/2259/2748/1700/2172/2314/1555/2964/2383/3840/3192/1820/2876/4491/1561/1624/18/45/1608/2408/3564/1649/2066/2538/1911/2273/2008 organoids for Azacitidine/Bleomycin sulfate/Bortezomib/Brigatinib/Cladribine/Clofarabine/Copanlisib/Cytarabine hydrochloride/Decitabine/DMSO/Doxorubicin hydrochloride/Everolimus/Gemcitabine hydrochloride/Idarubicin hydrochloride/Lenvatinib/Methotrexate/Mitomycin/Osimertinib/Oxaliplatin/Paclitaxel/Regorafenib/Sorafenib internal/Thioguanine/Topotecan hydrochloride/Triethylenemelamine/Valrubicin respectively. (b + c) Testing a wide variety of antimetabolites demonstrates a drug-specific on-target effect for antimetabolites in the same subclass as cladribine. No synergy between cladribine and lenvatinib was observed in HCCOs. n = 3 (different passages from one to two HCCO lines per named mouse cohort, technical duplicates; black/green/blue/magenta = HCCOs originated from tumours of cohort 5/19/20/23 respectively). Data shown as mean ± s.e.m. (d) In vitro dose-dependency testing of drug efficacy in murine HCCOs validates results from screen. n = 3 (different passages from one to two HCCO lines per named mouse cohort, technical duplicates). Data shown as mean ± s.e.m. (e) Representative images of dose-dependent drug effects on murine HCCOs after 9 days of treatment. Scale bar equals 200 µm. (f) In vitro dose-dependency testing of drug efficacy in human HCCOs validates results from screen. n = 3 (different passages from one to five human HCCO lines per driver combination, see methods for details, technical duplicates). Data shown as mean ± s.e.m.
