Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Nexus Between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer

Version 1 : Received: 24 December 2020 / Approved: 28 December 2020 / Online: 28 December 2020 (09:22:17 CET)

A peer-reviewed article of this Preprint also exists.

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. Cancers 2021, 13, 369.

Journal reference: Cancers 2021, 13, 369
DOI: 10.3390/cancers13030369

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.

Subject Areas

Breast cancer; Estrogen Receptor; PI3K-AKT-mTOR; anti-estrogen resistance

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.