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

Ningxin ZHANG; Li LI; Shan LIU; Jianyun NIE

doi:10.12259/j.issn.2095-610X.S20260401

Volume 47 Issue 4

Apr. 2026

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Ningxin ZHANG, Li LI, Shan LIU, Jianyun NIE. Advances in Squalene Epoxidase as A Potential Therapeutic Target in Breast Cancer[J]. Journal of Kunming Medical University, 2026, 47(4): 1-11. doi: 10.12259/j.issn.2095-610X.S20260401

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Ningxin ZHANG, Li LI, Shan LIU, Jianyun NIE. Advances in Squalene Epoxidase as A Potential Therapeutic Target in Breast Cancer[J]. Journal of Kunming Medical University, 2026, 47(4): 1-11. doi: 10.12259/j.issn.2095-610X.S20260401

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

doi: 10.12259/j.issn.2095-610X.S20260401

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 650108，China

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Corresponding author: 聂建云，博士，加拿大麦吉尔大学博士后，云南省肿瘤医院副院长，主任医师、博士研究生导师，深耕乳腺疾病诊疗领域30年。云南省兴滇英才计划“云岭名医”，获评“云南省有突出贡献优秀专业技术人才”、云南省中青年学术和技术带头人、云南省高层次人才医学学科带头人。国家卫健委国家级乳腺微创基地、云南省高校乳腺癌协同创新中心、乳腺癌转移与耐药机制研究创新团队、昆明医科大学一流学科优势团队负责人。中国肿瘤临床学会（CSCO）乳腺癌专家委员会常务委员、CSCO患者教育专家委员会副主任委员、中国抗癌协会整合肿瘤相关结节专业委员会副主任委员、中国健康促进基金会乳腺癌专委会副主任委员、云南省医师协会乳腺癌专业委员会主任委员。参与中国《CSCO乳腺癌诊疗指南》制定，牵头或参与19项乳腺癌相关指南及共识编撰，荣获全国“500最有影响力”医生称号。主持国家自然科学基金4项、省部级重点项目/重大科技专项5项，主持临床GCP研究90余项，获云南省科技进步一等奖、三等奖，云南省卫生科技成果二等奖；发表医学论文100余篇，其中SCI收录论文40余篇，主编医学专著5部、参编21部，获国家专利18项。
Received Date: 2025-12-31
Available Online: 2026-04-08
Publish Date: 2026-04-28

Abstract

Abstract

Breast cancer represents the most prevalent malignancy among women. The phenomenon of therapeutic resistance severely compromises patient prognosis, constituting a critical challenge that demands immediate resolution in clinical practice.Squalene epoxidase (SQLE), functioning as the rate-limiting enzyme within the cholesterol biosynthetic pathway, exhibits aberrant oncogenic expression in approximately 67% of breast cancer tissues. Elevated SQLE levels demonstrate significant correlations with advanced tumor grade, HER2-positive phenotypes, and unfavorable patient outcomes. Notably, within estrogen receptor-positive (ER+) breast cancer subtypes, high SQLE expression shows a marked association with endocrine therapy resistance.SQLE drives breast cancer progression and multidrug resistance through multiple molecular mechanisms, specifically including activation of the PI3K/AKT signaling cascade, suppression of tumor cell ferroptosis, and remodeling of the immunosuppressive microenvironment.Current evidence indicates that SQLE inhibitors (such as NB-598) and terbinafine both possess definitive antineoplastic activity. Moreover, when combined with targeted therapies or immunotherapy, these agents demonstrate potential for synergistic efficacy.Although SQLE has been validated as a significant target for prognostic assessment and therapeutic intervention, its clinical translation faces substantial obstacles. These challenges primarily encompass drug toxicity, variable efficacy across breast cancer molecular subtypes, and the lack of precise biomarkers for predicting therapeutic response.Therefore, future investigations should prioritize the development of highly selective SQLE-targeted therapeutics, optimization of combination regimens, and establishment of precision patient stratification systems based on SQLE expression profiles, thereby providing essential support for clinical application.
- SQLE,
- Breast cancer,
- Therapeutic resistance,
- PI3K/AKT pathway,
- Tumor microenvironment,
- Ferroptosis

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References(51)

References

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