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

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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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  1. Breast Cancer Program, Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 PRB, Nashville, TN, 37232-6307, USA

    Sara E. Nunnery & Ingrid A. Mayer

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

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Nunnery, S.E., Mayer, I.A. Targeting the PI3K/AKT/mTOR Pathway in Hormone-Positive Breast Cancer. Drugs 80, 1685–1697 (2020). https://doi.org/10.1007/s40265-020-01394-w

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