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Review
. 2020 Nov;80(16):1685-1697.
doi: 10.1007/s40265-020-01394-w.

Targeting the PI3K/AKT/mTOR Pathway in Hormone-Positive Breast Cancer

Sara E Nunnery  1 , Ingrid A Mayer  2
Affiliations
Review

Targeting the PI3K/AKT/mTOR Pathway in Hormone-Positive Breast Cancer

Sara E Nunnery et al. Drugs. 2020 Nov.

Abstract

Approximately 70% of invasive breast cancers have some degree of dependence on the estrogen hormone for cell proliferation and growth. These tumors have estrogen and/or progesterone receptors (ER/PR+), generally referred to as hormone receptor positive (HR+) tumors, as indicated by the presence of positive staining and varying intensity levels of estrogen and/or progesterone receptors on immunohistochemistry. Therapies that inhibit ER signaling pathways, such as aromatase inhibitors (letrozole, anastrozole, exemestane), selective ER modulators (tamoxifen), and ER down-regulators (fulvestrant), are the mainstays of treatment for hormone-receptor-positive breast cancers. However, de novo or acquired resistance to ER targeted therapies is present in many tumors, leading to disease progression. The PI3K/AKT/mTOR pathway is implicated in sustaining endocrine resistance and has become the target of many new drugs for ER+ breast cancer. This article reviews the function of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway and the various classes of PI3K pathway inhibitors that have been developed to disrupt this pathway signaling for the treatment of hormone-receptor-positive breast cancer.

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Conflict of interest statement

Conflicts of Interest: Ingrid Mayer receives institutional research funding from Novartis, Genentech, Pfizer and receives Advisory Board compensation from Novartis, Genentech, Lilly, Astra-Zeneca, GSK, Immunomedics, Macrogenics, Seattle-Genetics. Sara Nunnery has declared no conflicts of interest that might be relevant to the contents of this manuscript.

Figures

Figure 1:
Figure 1:
The PI3K/AKT/mTOR pathway
See this image and copyright information in PMC

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