PIK3CA and breast cancer: It has also been shown that dual targeting of Bcl-xL and PI3K in PIK3CA-mutant breast cancer models blocks tumor growth in vivo through modulation of mTOR-mediated Mcl-1 translation (20); this is consistent with our observation that blocking PI3K signaling (through genetic knockdown of AKT1 or MCL1) renders PIK3CA/PTEN-mutant TNBC models sensitive to Bcl-xL inhibitor–mediated radiosensitivity.