Heat maps showing average response within subtype (HER2⁺/PIK3CA^WT; HER2⁺/PIK3CA^mut; HER2^-) to targeted therapeutics alone and in combination from RPPA data.

<p><b>A</b>. Down-regulation of the PI3K-AKT pathway is evident in all HER2⁺ cells treated with lapatinib, irrespective of PI3K mutation status. However, the degree of down-regulation is less in cell lines with PI3K mutations (see p-S6 Ser235 for example). <b>B</b>. Treatment with GSK690693 leads to down-regulation of proteins downstream of AKT in all HER2⁺ cell lines, although the degree of down-regulation is less in lines harboring PI3K mutations. <b>C</b>. Treatment with the combination of lapatinib plus GSK690693 leads to down-regulation of the PI3K-AKT signaling pathway in both PIK3CA^mut and PIK3CA^WT lines. Note the much greater degree of down-regulation of S235 and S240 p-S6 in PIK3CA^mut cell lines treated with the combination relative to the single therapies. <b>D</b>. A summary of the most significant changes observed in the RPPA data for the PIK3CA^WT, PIK3CA^mut, and non-HER2 amplified cell lines under inhibition with lapatinib, GSK690693, or a combination of the two.