Next Article in Journal
High-Content Analysis-Based Sensitivity Prediction and Novel Therapeutics Screening for c-Met-Addicted Glioblastoma
Next Article in Special Issue
Amongst Women Stratified to Receive Endocrine Therapy on the Basis of Their Tumor Estrogen and Progesterone Receptor Levels, Those with Higher Tumor Progesterone Receptor Levels Had a Better Outcome Than Those with Lower Levels of Tumor Progesterone Receptor
Previous Article in Journal
HER2-Positive Breast Cancer Patients with Pre-Treatment Axillary Involvement or Postmenopausal Status Benefit from Neoadjuvant Rather than Adjuvant Chemotherapy Plus Trastuzumab Regimens
Previous Article in Special Issue
Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients
Open AccessReview

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

1
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3
VA Roudebush Medical Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Christos Papadimitriou, Dimitrios Mavroudis and Nicholas Pavlidis
Cancers 2021, 13(3), 369; https://doi.org/10.3390/cancers13030369
Received: 24 December 2020 / Revised: 12 January 2021 / Accepted: 15 January 2021 / Published: 20 January 2021
(This article belongs to the Special Issue Estrogen Receptor-Positive (ER+) Breast Cancers)
Breast cancers are broadly classified into two subtypes: estrogen receptor-positive and estrogen receptor-negative. Approximately 70% of breast cancers are estrogen receptor-positive and this type of breast cancer is more common in postmenopausal women. Estrogen receptor-positive breast cancers are treated with a class of drugs called anti-estrogens. While the majority of tumors respond to this class of drugs, disease recurs in approximately 30% of cases, sometimes even 20 years after initial diagnosis. This review highlights efforts to understand why tumors recur despite effective treatments and outcome of these efforts in the development of new combination therapies. At least three new types of combination therapies that delay progression of recurrent tumors are in clinical use.
Signaling from estrogen receptor alpha (ERα) and its ligand estradiol (E2) is critical for growth of ≈70% of breast cancers. Therefore, several drugs that inhibit ERα functions have been in clinical use for decades and new classes of anti-estrogens are continuously being developed. Although a significant number of ERα+ 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 ERα signaling, and interplay between cell cycle machinery and ERα signaling. ESR1 mutations as well as crosstalk with other signaling networks lead to ligand independent activation of ERα thus rendering anti-estrogens ineffective, particularly when treatment involved anti-estrogens that do not degrade ERα. As a result of these studies, several therapies that combine anti-estrogens that degrade ERα with PI3K/AKT/mTOR inhibitors targeting growth factor signaling or CDK4/6 inhibitors targeting cell cycle machinery are used clinically to treat recurrent ERα+ breast cancers. In this review, we discuss the nexus between ERα-PI3K/AKT/mTOR pathways and how understanding of this nexus has helped to develop combination therapies. View Full-Text
Keywords: breast cancer; estrogen receptor; PI3K-AKT-mTOR; anti-estrogen resistance breast cancer; estrogen receptor; PI3K-AKT-mTOR; anti-estrogen resistance
Show Figures

Graphical abstract

MDPI and ACS Style

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. https://doi.org/10.3390/cancers13030369

AMA Style

Khatpe AS, Adebayo AK, Herodotou CA, Kumar B, Nakshatri H. Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers. 2021; 13(3):369. https://doi.org/10.3390/cancers13030369

Chicago/Turabian Style

Khatpe, Aditi S.; Adebayo, Adedeji K.; Herodotou, Christopher A.; Kumar, Brijesh; Nakshatri, Harikrishna. 2021. "Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer" Cancers 13, no. 3: 369. https://doi.org/10.3390/cancers13030369

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop