71 Novel regulation of estrogen receptor transcription by the PI3K pathway Academic Article uri icon


  • Results: We have identified gain-of-function genomic alterations in AKT3 associated with therapy refractoriness in HER2-amplified breast cancer patients treated with anti-HER2 agents in a chemotherapy-free setting. Specifically, copy-gain and genomic mutation were associated with intrinsic resistance to trastuzumab or lapatinib. Protein modeling predicts an activating role for the mutation identified, providing a mechanism for pathway activation beyond those previously described. Treatment combination with specific AKT inhibitors might improve treatment efficacy and overcome resistance to HER2-directed therapy. Conclusions: Genomic analyses of selected patient biopsies provide relevant biomarkers that can be used for clinical decision making. The involvement of AKT3 in the development of resistance to anti-HER2 agents provides an actionable target for efficient therapeutic …

publication date

  • January 1, 2014