AKT1 and brain neoplasm: Of note, AKT and ERK phosphorylation were enhanced in MDA-MB-361 tumors (Supplemental Fig. 1I),5 an effect that was stronger when macitentan was added to T-DM1 (Supplemental Fig. 1I).5 The underlying mechanisms of the increased signaling in response to dual endothelin-receptor inhibition in MDA-MB-361 brain tumors remain unclear.