Khatpe, A.S.; Adebayo, A.K.; Herodotou, C.A.; Kumar, B.; Nakshatri, H. Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers2021, 13, 369.
Khatpe, A.S.; Adebayo, A.K.; Herodotou, C.A.; Kumar, B.; Nakshatri, H. Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers 2021, 13, 369.
Khatpe, A.S.; Adebayo, A.K.; Herodotou, C.A.; Kumar, B.; Nakshatri, H. Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers2021, 13, 369.
Khatpe, A.S.; Adebayo, A.K.; Herodotou, C.A.; Kumar, B.; Nakshatri, H. Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers 2021, 13, 369.
Abstract
Signaling from estrogen receptor alpha (ER) and its ligand estradiol (E2) is critical for growth of ~70% of breast cancers. Therefore, several drugs that inhibit ER functions are in clinical use for decades and new classes of anti-estrogens are continuously being developed. Although a significant number of ER+ breast cancers respond to anti-estrogen therapy, ~30% of these breast cancers recur, sometimes even after 20 years of initial diagnosis. Mechanism of resistance to anti-estrogens is one of the intensely studied disciplines in breast cancer. Several mechanisms have been proposed including mutations in ESR1, crosstalk between growth factor and ER signaling, and interplay between cell cycle machinery and ER signaling. ESR1 mutations as well as crosstalk with other signaling networks lead to ligand independent activation of ER thus rendering anti-estrogens ineffective, particularly when treatment involved anti-estrogens that do not degrade ERa. As a result of these studies, several therapies that combine anti-estrogens that degrade ER with PI3K/AKT/mTOR inhibitors targeting growth factor signaling or CDK4/6 inhibitors targeting cell cycle machinery are used clinically to treat recurrent ER+ breast cancers. In this review, we discuss nexus between ER-PI3K/AKT/mTOR pathways and how understanding of this nexus has helped to develop combination therapies.
Keywords
Breast cancer; Estrogen Receptor; PI3K-AKT-mTOR; anti-estrogen resistance
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
