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Comment
. 2021 Feb 1;81(3):537-538.
doi: 10.1158/0008-5472.CAN-20-4037.

The ESR1 Mutations: From Bedside to Bench to Bedside

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Comment

The ESR1 Mutations: From Bedside to Bench to Bedside

Francisco Hermida-Prado et al. Cancer Res. .

Abstract

The ESR1 ligand-binding mutations were unveiled a number of years ago and are the most common genetic mechanism of acquired resistance to endocrine treatment, particularly, to aromatase inhibitors. The discovery of these mutations was enabled after advancements in sequencing technologies and when metastatic tissue samples were interrogated. The ESR1 ligand-binding domain mutations are activating mutations that lead to constitutive ligand-independent activity, which explains the emergence of these mutations under the selective pressure of aromatase inhibitors. Arnesen and colleagues have generated new models of the ESR1 mutations using CRISPR technology to generate single-cell-derived clones in which the ESR1 ligand-binding mutations were "knocked-in" and expressed under the endogenous promoter of estrogen receptor. The authors have extensively characterized these models and have shed new light on the functional consequences ESR1 mutations.See related article by Arnesen et al., p. 539.

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References

    1. Razavi P, Chang MT, Xu G, Bandlamudi C, Ross DS, Vasan N, et al. The genomic landscape of endocrine-resistant advanced breast cancers. Cancer Cell. 2018;34:427–38.
    1. Jeselsohn R, De Angelis C, Brown M, Schiff R. The evolving role of the estrogen receptor mutations in endocrine therapy-resistant breast cancer. Curr Oncol Rep. 2017;19:35.
    1. Toy W, Weir H, Razavi P, Lawson M, Goeppert AU, Mazzola AM, et al. Activating ESR1 mutations differentially affect the efficacy of ER antagonists. Cancer Discov. 2017;7:277–87.
    1. Kuang Y, Siddiqui B, Hu J, Pun M, Cornwell M, Buchwalter G, et al. Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer. NPJ Breast Cancer. 2018;4:22.
    1. Zundelevich A, Dadiani M, Kahana-Edwin S, Itay A, Sella T, Gadot M, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020;22:16.

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