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. 2023 Jul 14;14:4221. doi: 10.1038/s41467-023-40022-5

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© The Author(s) 2023

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — A In vivo response to IACS-010759 treatment in PDX of ER + BM. Mean ± SD. HBCx-124: n = 3 mice (control) and 4 mice (IACS and fulvestrant). HBCx-118: n = 4 mice/group. HBCx-202: n = 6 mice/group. HBCx-134 n = 5 mice (control and IACS) and n = 8 mice (fulvestrant). P values were calculated with the Mann–Whitney test (two-tailed). B Response of HBCx-124 to different doses of IACS-010759 and to metformin (n = 7 mice/group) P values were calculated with the Mann–Whitney test (two-tailed). C GSEA analysis of HBCx-124 xenografts after 1 week of IACS treatment. D Establishment of the palbociclib-resistant HBCx-124 palboR25 PDX model. E Enrichment plots of oxidative phosphorylation, TFAM target genes and respiratory electron transport hallmarks from the GSEA enrichment analysis of HBCx-124 palboR25 PDX as compared to the parental palbo responder (palbo S) HBCx-124. NES normalised enrichment score. FDR false discovery rate. Oxidative phosphorylation heatmap. F Kaplan–Meier survival analysis of HBCx-124 palboR25 PDX treated by fulvestrant and palbociclib, IACS-010759 and the combination of palbociclib + fulvestrant and IACS-010759 n = 6 mice (control), n = 7 mice (fulv palbo and IACS, n = 5 mice (IACS + palbo fulv). Log-rank (Mantel–Cox) test. G Establishment of the palbociclib-resistant HBCx-134 palboR31 PDX model. H Enrichment plots of oxidative phosphorylation, NES normalised enrichment score, FDR false discovery rate. Oxidative phosphorylation heatmap. I Response to IACS, fulvestrant and palbo and IACS + fulvestrant and palbo in the HBCx-134 palbo31 PDX. n = 4 mice (control), n = 5 mice (IACS, palbo fulv), n = 6 mice (IACS + palbo fulv). Mean ± SD. RTV relative tumour volume. Source data are provided as a Source Data file. n number of mice.