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Fig. 7 | Breast Cancer Research

Fig. 7

From: Sensitivity to targeted therapy differs between HER2-amplified breast cancer cells harboring kinase and helical domain mutations in PIK3CA

Fig. 7

Addition of NRG1β de-sensitizes cells to lapatinib, co-treatment with AKT inhibitor or pertuzumab overcomes this effect. A Parental SKBR3 cells or PIK3CA mutant clones treated with lapatinib, AKT inhibitor GSK690693, or combination of the two drugs at a fixed molar ratio in the absence or presence of NRG1β for 72 h. Only H1047R knockin mutant cells show decreased sensitivity to lapatinib at baseline, consistent with results shown in Fig. 1. Treatment with NRG1β makes cells more resistant to lapatinib, and response is partially restored by co-treatment with GSK690693. The efficacy of the combination is greatest in the H1047R mutant cells as measured by the GRmax response. Significant synergistic interactions are marked with an *. B Parental SKBR3 cells or PIK3CA mutant clones treated with lapatinib, pertuzumab, or combination of the two drugs at a fixed molar ratio in the absence or presence of NRG1β for 72 h. Combination of drugs resulted in synergistic growth inhibition at low doses in all three cell lines, but offered no benefit over lapatinib alone at higher doses. Addition of NRG1β-induced resistance to lapatinib in all three cell lines was abrogated with the addition of pertuzumab. Note that synergy could not be accurately calculated by the combination index method for these curves since it requires fitting dose-response curves and pertuzumab did not have any effect on the growth of cells as a monotherapy

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