Work

ESR1 activating mutations: From structure to clinical application

Year: 2022

Type: article

Abstract: Estrogen receptor-positive breast cancer is the most common type of both early and advanced breast cancer. Estrogen receptor alpha (ER) is a nuclear hormone receptor and a key driver of tumorigenesis and tumor progression in these breast cancers. As such, it is a key treatment target and a biomarker predictive of response to endocrine therapy. Activating ESR1 ligand binding domain mutations engender constitutive/ligand independent transcriptional activities and emerge following prolonged first-line hormone therapy regimens, mainly from aromatase inhibitors. The full scale of the biological and clinical significance of these mutations continue to evolve and additional studies are required to further discern the multimodal effects of these mutations on ER transcription, metastatic propensity, and the tumor microenvironment. Furthermore, recent and ongoing studies highlight the potential clinical utility of these mutations as therapeutic targets and dynamic biomarkers. Herein, we review the structure, functional consequences, and clinical implications of the activating ESR1 mutations in advanced estrogen receptor-positive breast cancer.

Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

DOI: 10.1016/j.bbcan.2022.188830

Authors: Albert Grinshpun, Vincent Chen, Zachary M. Sandusky, Sean W. Fanning, Rinath Jeselsohn

Institutions: Dana-Farber Cancer Institute, Loyola University Chicago, Dana-Farber/Harvard Cancer Center

Language: English

Topic: Estrogen and related hormone effects

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,740