Interactions of PI3K/Akt/mTOR and estrogen receptor signaling in breast cancer

Abstract

SUMMARY Endocrine therapies are used to treat estrogen receptor-positive (ER+) breast cancer; however, patients develop resistance in some cases due to hormone-independent activation of ER signaling. Dysregulation of mTOR, a central hub for various signaling pathways regulated by hormones and growth factors, is a mechanism of endocrine therapy resistance. Activation of kinases in these pathways can cause ligand-independent ER signaling. Phosphorylation of ER regulates activity and predicts clinical outcome in ER+ breast cancer. PI3K/Akt/mTOR pathway activation in breast cancer is common and considered a therapeutic target. PI3K/Akt/mTOR signaling is complex and interacts with ER signaling. mTOR’s downstream target p70S6K negatively regulates Akt on one hand and can phosphorylate ER. Moreover, overexpressed p70S6K activates ER in breast cancer cells. An overall understanding of signaling events, especially those governed by mTOR, is important in deciding treatment protocols for ER+ breast cancers.