Estrogen receptor α36 in female estrogen-related tumors:regulatory mechanisms and targeted therapeutic advances
10.12354/j.issn.1000-8179.2025.20250639
- VernacularTitle:雌激素受体α36在女性雌激素相关肿瘤中的调控机制与靶向治疗研究进展
- Author:
Zhang LILI
1
;
Wang LIRONG
;
Yuan YUE
;
Ma XIAOLING
Author Information
1. 兰州大学核科学与技术学院(兰州市 730000);兰州大学第一医院生殖医学中心
- Publication Type:Journal Article
- Keywords:
estrogen receptor α36(ERα36);
estrogen receptor;
tumor;
targeted therapy
- From:
Chinese Journal of Clinical Oncology
2025;52(16):848-853
- CountryChina
- Language:Chinese
-
Abstract:
Estrogen receptor α36(ERα36),a splice variant of ERα66,is crucial in the pathogenesis,progression,and therapeutic resistance of female estrogen-related tumors(e.g.,breast,cervical,and endometrial cancers)as it uniquely activates non-genomic signaling pathways.This review provides a comprehensive summary of the structural features of ERα36 and its molecular mechanisms in regulating tumor prolif-eration,migration,and drug resistance via membrane-mediated pathways,including phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)and mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK).The interaction between ERα36 and epi-dermal growth factor receptor/human epidermal growth factor receptor2(EGFR/HER2)forms a positive feedback loop that exacerbates ma-lignant transformation.High ERα36 expression is associated with decreased sensitivity to chemotherapy and resistance to tamoxifen.Recent studies have demonstrated that natural compounds and synthetic inhibitors targeting ERα36 can reverse drug resistance and suppress can-cer stem cell activity by blocking non-genomic signaling.This review provides novel insights into overcoming drug resistance and optimizing targeted therapies for female estrogen-related malignancies.
