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. 2022 Apr 1;24:23. doi: 10.1186/s13058-022-01521-3

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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. 5 — Dual PI3K/SHP2 inhibition blocks 3D organoid formation in two patient-derived breast cancer models and tumor growth in a xenograft model. a Representative images of organoids grown from patient-derived PIK3CA mutant HBCx4B TNBC cells after 10 days of treatment with BYL719, SHP099 or the combination thereof with the indicated concentrations. Magnification: 400×. b Normalized quantification of HBCx4B organoid formation in (a). Organoid diameter of 40 μm was taken as cut-off. Inhibition of organoid formation in the BYL719/SHP099 combination treatment is significant (p ≤ 0.01), calculated by one-way ANOVA. Experiment was performed on two biological replicates. c Normalized luminescence after CellTiter-Glo cell viability assay on the HBCx4B organoids of (a). Organoids treated with BYL719/SHP099 have significantly lower luminescence (p ≤ 0.01) compared to the monotreatments, calculated by one-way ANOVA. RLU: Relative Light Unit. Experiment was performed on three biological replicates. d Average tumor volume over time in nude mice injected with 2 × 10⁶ HCC1806 cells, treated with either vehicle, 15 mg/kg BYL719, 75 mg/kg SHP099 or the combination of 15 mg/kg BYL719 + 75 mg/kg SHP099. Three mice per group were treated daily starting at day 10 after injection. Inhibition of tumor growth in the BYL719/SHP099 combination treatment is significant (p ≤ 0.05), calculated by one-way ANOVA