角鲨烯环氧化酶作为乳腺癌治疗潜在靶点的研究进展

张宁鑫; 李莉; 刘珊; 聂建云

角鲨烯环氧化酶作为乳腺癌治疗潜在靶点的研究进展

张宁鑫¹,
李莉²,
刘珊^{1, 2},
聂建云^1, ,

1.
昆明医科大学第二附属医院甲状腺乳腺外科，云南昆明　650101
2.
昆明医科大学第三附属医院乳腺二科，云南昆明　650100

详细信息

作者简介:
张宁鑫（1987～），男，云南永胜人，医学硕士，主治医师，主要从事乳腺甲状腺研究工作

通讯作者:
聂建云，E-mail：niyvip@sina.com

中图分类号: R737.9
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- 文章访问数: 2
- HTML全文浏览量: 1
- PDF下载量: 0
- 被引次数: 0
出版历程
- 网络出版日期: 2026-04-08

Advances in Squalene Epoxidase as A Potential Therapeutic Target in Breast Cancer

Ningxin ZHANG¹,
Li LI²,
Shan LIU^{1, 2},
Jianyun NIE^{1
, ,}

1.
Department of Thyroid and Breast Surgery，The Second Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101
2.
Department of Breast Surgery Ⅱ，The Third Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650100，China

摘要

摘要: 腺癌是女性最常见恶性肿瘤，治疗耐药严重影响预后。角鲨烯环氧化酶（squalene epoxidase，SQLE）作为胆固醇合成关键酶，以癌基因形式在约67%乳腺癌中高表达，与肿瘤分级、HER2阳性及不良预后相关，尤其在ER+型中与内分泌耐药密切相关。其通过激活PI3K/AKT通路、抑制铁死亡、重塑免疫抑制微环境等，推动肿瘤进展及多药耐药。SQLE抑制剂（如NB-598）及特比萘芬具抗肿瘤活性，联合靶向或免疫治疗有协同潜力。目前其临床转化面临毒性、亚型差异及标志物缺乏等挑战，SQLE是乳腺癌预后评估和治疗的重要靶点，未来需开发高选择性药物、优化联合方案并建立精准分层体系。
- 角鲨烯环氧化酶 /
- 乳腺癌 /
- 治疗耐药 /
- PI3K/AKT通路 /
- 肿瘤微环境 /
- 铁死亡
Abstract: ［Abstract］ Breast cancer is the most common malignant tumor in women, with treatment resistance severely affecting prognosis. Squalene epoxidase （SQLE）, a key enzyme in cholesterol biosynthesis, is highly expressed as an oncogene in approximately 67% of breast cancers and is associated with tumor grade, HER2 positivity, and poor prognosis, particularly closely related to endocrine resistance in ER-positive subtypes. SQLE promotes tumor progression and multidrug resistance through activating the PI3K/AKT pathway, inhibiting ferroptosis, and remodeling of the immunosuppressive microenvironment. SQLE inhibitors （such as NB-598） and terbinafine demonstrate antitumor activity, with synergistic potential when combined with targeted or immunotherapies. Currently, clinical translation faces challenges including toxicity, subtype heterogeneity, and lack of biomarkers. SQLE represents an important target for prognosis assessment and treatment of breast cancer. Future directions require development of highly selective drugs, optimization of combination regimens, and establishment of precision stratification systems.
- SQLE /
- Breast cancer /
- Therapeutic resistance /
- PI3K/AKT pathway /
- Tumor microenvironment /
- Ferroptosis

HTML全文

图 1 SQLE 调控 ER stress/WIP1/ATM 及 PI3K/AKT 通路介导乳腺癌耐药机制图

Figure 1. SQLE-mediated breast cancer resistance via regulating ER stress/WIP1/ATM and PI3K/AKT pathways

下载: 全尺寸图片幻灯片

图 2 SQLE 通过经典与旁路胆固醇代谢调控肿瘤代谢重编程及训练免疫的机制示意图

Figure 2. SQLE regulating tumor metabolic reprogramming and trained immunity via canonical and alternative cholesterol metabolism

下载: 全尺寸图片幻灯片

图 3 SQLE 通过 PI3K/AKT 信号轴及肿瘤免疫微环境调控乳腺癌进展机制示意图

A：PI3K/AKT 信号通路调控；B：肿瘤免疫微环境调控（免疫检查点）；C：肿瘤免疫微环境调控（铁死亡逃逸）。

Figure 3. SQLE regulating breast cancer progression via PI3K/AKT signaling axis and tumor immune microenvironment

下载: 全尺寸图片幻灯片

图 4 SQLE 通过调控胆固醇代谢及信号通路介导乳腺癌多药耐药的核心机制示意图

Figure 4. Core mechanism of SQLE in mediating multidrug resistance in breast cancer via regulating cholesterol metabolism and signaling pathways

下载: 全尺寸图片幻灯片

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