Addition of the p110 α inhibitor BYL719 overcomes targeted therapy resistance in cells from Her2-positive-PTEN-loss breast cancer

In this study, we established an HER2-positive and PTEN loss cell line and confirmed it by western blot analysis. This cell line and its orthotopic xenograft models were exposed to p110 α-specific inhibitor BYL719, p110β-specific inhibitor AZD6482, or pan-PI3K inhibitor BKM120, respectively, and the results showed sensitivity to both BYL719 and BKM120 but not AZD6482, which indicated a p110α-reliance for HER2-positive-PTEN-loss breast cancer. Then, the addition of BYL719 to HER2 antibody greatly reduced tumor growth both in vitro and in vivo, accompanied by inhibited PI3K effector phosphorylation. Therefore, our findings suggest that the combination of p110α-selective inhibitor BYL719 with HER2 antibody could be a potential strategy for more personalized treatment of HER2 -posistive-PTEN-loss breast cancer; and in addition, the optimal schedule of this combination therapy needs to be further explored.
Source: Tumor Biology - Category: Cancer & Oncology Source Type: research