Figure 2.

Estrogen receptor-α (ERα) can be directly activated, by serine phosphorylation at Ser-118 and Ser-167, by mitogen-activated protein kinase (MAPK) and Akt respectively, through growth factor signaling. This can result in the ligandless activation of ERα and hormone resistance. Clinical trials of combinations of signaling inhibitors and hormonal agents are needed to investigate whether signaling blockade can enhance hormone resistance.