2022 年第 10 期 第 17 卷

Notch受体调控乳腺癌细胞中雌激素相关受体表达影响内分泌治疗抵抗的研究进展

Research progress of Notch receptor regulating estrogen-related receptor expression in breast cancer cells and affecting endocrine therapy resistance

作者：王玉洁杜瀚林王志伟李鸿涛

英文作者：Wang Yujie Du Hanlin Wang Zhiwei Li Hongtao

单位：新疆医科大学附属肿瘤医院乳腺甲状腺外科，乌鲁木齐830011

英文单位：Department of Breast and Thyroid Surgery Cancer Hospital Affiliated to Xinjiang Medical University Urumqi 830011 China

关键词：乳腺癌；内分泌治疗抵抗；Notch受体；雌激素受体

英文关键词：Breastcancer;Resistancetoendocrinetherapy;Notchreceptor;Estrogenreceptor

• 摘要：

• 研究表明近70%的乳腺癌均表达雌激素受体(ER)，并且肿瘤细胞增殖和存活具有激素依赖性。芳香化酶抑制剂、选择性ER调节剂或选择性ER下调调节剂的抗雌激素治疗是ER阳性乳腺癌患者的标准内分泌治疗方法 。然而，大约30%的接受内分泌治疗的患者会在治疗期间进展或最终形成内分泌抵抗。内源性或获得性内分泌抵抗已成为内分泌治疗的主要障碍。内分泌抵抗的机制非常复杂。最新研究证据表明Notch信号通路通过决定血管生成的Notch受体和配体的过度表达和/或异常遗传型表达的失调导致了乳腺癌患者的内分泌抵抗，其潜在的机制包括调节ER，促进肿瘤干细胞表型和间充质细胞比例，影响肿瘤微环境和细胞周期，最终导致内分泌治疗耐药的形成。本文就Notch受体活性影响乳腺癌细胞中雌激素相关受体的表达导致内分泌治疗抵抗的研究进展进行综述。

• Studies have shown that nearly 70% of breast cancers express estrogen receptor(ER), and tumor cell proliferation and survival are hormone-dependent. Antiestrogen therapy with aromatase inhibitors, selective ER modulators, or selective ER downregulators is the standard endocrine therapy for patients with ER-positive breast cancer. However, approximately 30% of patients receiving endocrine therapy progress or eventually develop endocrine resistance during treatment. Endogenous or acquired endocrine resistance has become a major obstacle to endocrine therapy. The mechanism of endocrine resistance is very complex. Recent evidence suggests that the Notch signaling pathway contributes to endocrine resistance in breast cancer patients through overexpression and/or dysregulation of abnormal genotypic expression of Notch receptors and ligands that determine angiogenesis. The underlying mechanisms include regulation of ER and promotion of cancer stem cells phenotype and mesenchymal cell ratio, influence the tumor microenvironment and cell cycle, and ultimately lead to the development of endocrine therapy resistance. This article reviews the research progress of Notch receptor activity affecting the expression of estrogen-related receptors in breast cancer cells leading to resistance to endocrine therapy.