PIK3CA is the most frequently mutated oncogene in cancer and PI3K inhibitors are now a standard treatment in PIK3CA mutant ER+ metastatic breast cancer. In this lecture I will discuss our discovery of double mutant PIK3CA, which functions as a hypermorphic oncogene and results in increased sensitivity to PI3K inhibitors in breast cancer, compared to single mutant PIK3CA. Our studies establish double mutations as a novel mechanism of oncogenesis, leading to a mutational dosage model for the activation and inhibition of oncogenic PI3K. Further dissection of this model will yield new mechanistic insights to broaden the scope of PI3K inhibitors in cancer.
(Refreshments will be served at 3:45 pm)