Figure 3.

Synergy of PI3K inhibitors plus trastuzumab is specific for PI3K pathway alteration-related resistance. A. Alpelisib plus trastuzumab and GDC-0077 plus trastuzumab both exhibit synergistic effects (CI <1) in resistant breast cancer cells. B. HCC1954 cells were transiently transfected with siRNA resulting in PTEN knockdown. The combination strategy with one PI3K inhibitor and trastuzumab still results in prominent antiproliferative effects in HCC1954 cells exhibiting a partial loss of PTEN protein. Experiments were repeated in triplcate and the results are summarized as bar charts representing the mean ± SD. P-value: *P<0.05, **P<0.01, ***P<0.001, and ****P<0.0001. C. CK-MB-1 cells are neither PIK3CA mutant nor PTEN deficient. PI3K inhibitors or trastuzumab showed no efficacy in CK-MB-1 cells either as monotherapy or in combination.