In addition, we found that triple combination with the dual PI3K/mTORi gedatolisib, the recent evaluation of which in a phase 1b clinical trial in combination with CDK4/6i and endocrine therapy demonstrated tolerability and preliminary efficacy in ER+ advanced breast cancer patients39, showed comparable efficacy to the triple combination with AKTi in inhibiting the growth of cell lines resistant to combined CDK4/6i and fulvestrant. This evidence concerns the gene ESR1 and breast carcinoma.