雌激素受体
芳香化酶
雌激素受体α
乳腺癌
癌症研究
雌激素
芳香化酶抑制剂
雌激素受体
癌变
癌症
生物
生物标志物
医学
生物信息学
内科学
肿瘤科
遗传学
作者
Albert Grinshpun,Vincent Chen,Zachary M. Sandusky,Sean W. Fanning,Rinath Jeselsohn
标识
DOI:10.1016/j.bbcan.2022.188830
摘要
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.
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