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. 2022 Mar 10;41:89. doi: 10.1186/s13046-022-02301-9

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 7 — The PDO subtypes based on niche factor dependency show distinct drug treatment responses. A Heatmap of expression levels on the genes of mevalonate pathway–related enzymes in PDOs (left). Simplified overview of the mevalonate pathway (right). Upregulated enzymes in PDOs with high niche dependency are shown in red. B Representative images of PDOs treated with the indicated concentration of gemcitabine for 72 h after 7 days’ culture in combined medium. Scale bars, 200 µm. C Dose–response curve of PDOs treated with gemcitabine for 72 h. Results were normalized using the proliferation of PDOs treated with gemcitabine 0.001 nM as 100% response. D AUC distribution of gemcitabine sensitivity in the “High” and “Low” niche dependency subtypes (**P < 0.01). E Spearman’s correlation analysis between niche dependency and sensitivity to gemcitabine. F Representative images of PDOs cultured in combined medium with the indicated concentration of simvastatin for 10 days. Scale bars, 200 µm. G Dose–response curve of PDOs treated with simvastatin for 10 days. Results are normalized according to the proliferation of PDOs treated with simvastatin 0.001 nM as 100% response. H AUC distribution of simvastatin sensitivity in the “High” and “Low” niche dependency subtypes (*P < 0.05). I Spearman’s correlation analysis between niche dependency and sensitivity to simvastatin. J Representative images of PDO573 treated with the indicated concentration of gemcitabine for 72 h after 7 days’ culture in serum medium or combined medium. Scale bars, 200 µm. K Dose–response curve of PDO573 treated with gemcitabine for 72 h. Results were normalized using the proliferation of PDO573 treated with gemcitabine 0.001 nM as 100% response. L Representative images of PDO573 cultured in serum medium or combined medium with the indicated concentration of simvastatin for 10 days. Scale bars, 200 µm. M Dose–response curve of PDOs treated with simvastatin for 10 days. Results are normalized according to the proliferation of PDOs treated with simvastatin 0.001 nM as 100% response