Experiments using breast cancer cell lines carrying PI3Kα mutations and therefore resistant to the specific PI3Kα- inhibitor BYL719, revealed that the observed residual mTORC1 activity was PtdIns(3,4,5)P3- and thus AKT- independent, and stands in need of both PIF-binding pocket and kinase activity of PDK1. The gene discussed is PDK1; the disease is breast cancer.