In an effort to understand the molecular predictors of response to GDC-0941, we determined whether key alterations in the PI3K pathway such as HER2 amplification, PIK3CA mutations, or PTEN loss (protein null by Western blotting) were associated with greater sensitivity to GDC-0941....We found that cell lines harboring oncogenic mutations in PIK3CA, or HER2 amplification, were significantly more sensitive than cell lines without these alterations (P = 0.005 PIK3CA versus WT, P = 0.048 HER2 versus WT; Fig. 1C). In addition, we found that cell lines harboring double alterations in PIK3CA and HER2, PIK3CA and PTEN, or HER2 and PTEN were common and were all significantly more sensitive than cell lines with no detectable alterations in the signaling pathway (P = 0.009, double mutants versus none).