TSC2 and breast cancer: We next tested whether Mcl-1 inhibition using AZD5991 is effective at overcoming PI3Ki and AKTi inhibitor resistance in PTEN-null breast cancer cells lacking PI3KR2, INPPL1 and TSC2. In PIK3R2 and INPPL1 KO cells (where AZD8186 resistance in caused by sustained AKT signaling) the combination of AZD8186 and AZD5991 was ineffective, but the combination of capivasertib and AZD5991 was still effective (Fig. 5A, C and Supplementary Fig. 4A, B).