Our study shows that gedatolisib, an equipotent pan-PI3K/mTOR inhibitor well tolerated in patients, is more effective at inhibiting PAM pathway functions than single-node PAM inhibitors such as alpelisib (PI3Kα), capivasertib (AKT) and everolimus (mTORC1), and induces greater growth-inhibitory and cytotoxic activity in BC cells with altered or wild type PAM pathway status. The gene discussed is AKT1; the disease is breast cancer.