Fig. 7.

Proposed models for illustrating potential molecular mechanisms altered by PIK3CA^H1047R in HER2⁺ (a) or ER⁺ (b) breast cancer. a Hypo-phosphorylation of EGFR altered by PIK3CA^H1047R may correlate with potential resistance of pan-ERBB inhibitors (e.g., Lapatinib) due to PI3K-mediated feedback repression of ERBB family proteins as described in the previous studies [40, 41]. b Elevated phosphorylation level of YAP (“Hippo on”) is a common feature in ER⁺PIK3CA^H1047R breast cancer compared to ER⁺ PIK3CA^WT. This may contribute to the potential activation of MAPK and STAT3 pathways and further correlate with the sensitivity of MEK/MAPK inhibitors