← 返回

整合分子靶向与免疫调节在三阴性乳腺癌中的应用:从机制洞察到治疗创新

英文原题:Integrating molecular targeting and immune modulation in triple-negative breast cancer: from mechanistic insights to therapeutic innovation.

查看英文原题

Integrating molecular targeting and immune modulation in triple-negative breast cancer: from mechanistic insights to therapeutic innovation.

PubMed 2025/11/26(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

三阴性乳腺癌(TNBC)仍然是乳腺癌中一种临床侵袭性亚型,其特征为雌激素受体、孕激素受体和HER2扩增均缺失,且对年轻人和不同种族人群的影响尤为显著。尽管采用常规化疗,TNBC患者由于缺乏可操作的分子靶点及早期转移潜能,往往面临不良预后。分子谱分析的进展揭示了不同的TNBC亚型及可操作的脆弱性,包括BRCA1/2突变和PI3K/AKT/mTOR信号通路失调。靶向DNA修复通路、血管生成和雄激素受体信号传导的治疗——特别是通过PARP抑制剂和抗体药物偶联物如sacituzumab govitecan——已显示出临床获益。与此同时,TNBC的免疫原性特征,表现为密集的TIL(肿瘤浸润淋巴细胞)(TILs),推动了免疫检查点抑制剂的整合应用。

然而,原发性和获得性耐药仍是主要障碍。本综述阐述了靶向治疗和免疫治疗策略的最新进展,强调TILs在塑造治疗反应中的作用,并着重介绍将分子靶向与免疫调节协同作用的联合方案。通过全面理解TNBC的分子和免疫景观,我们提出新的治疗路径,以改善这一具有挑战性的恶性肿瘤的临床结局。

展开英文摘要原文

Triple-negative breast cancer (TNBC) remains a clinically aggressive subtype of breast cancer, defined by the absence of estrogen receptor, progesterone receptor, and HER2 amplification, and disproportionately affecting younger and racially diverse populations. Despite conventional chemotherapy, TNBC patients often face poor prognoses due to the lack of actionable molecular targets and early metastatic potential.

Advances in molecular profiling have unveiled distinct TNBC subtypes and actionable vulnerabilities, including BRCA1/2 mutations and PI3K/AKT/mTOR dysregulation. Therapies targeting DNA repair pathways, angiogenesis, and androgen receptor signaling-particularly via PARP inhibitors and antibody-drug conjugates like sacituzumab govitecan-have demonstrated clinical benefit. Concurrently, TNBC's immunogenic nature, reflected in dense tumor-infiltrating lymphocytes (TILs), has driven the integration of immune checkpoint inhibitors.

However, both primary and acquired resistance remain major barriers. This review delineates recent developments in targeted and immunotherapeutic strategies, emphasizing the role of TILs in shaping treatment response and highlighting combinatorial approaches that synergize molecular targeting with immunomodulation. Through a comprehensive understanding of TNBC's molecular and immune landscape, we propose new therapeutic trajectories to improve clinical outcomes in this challenging malignancy.

论文信息

作者
Fan Y、Wang H、Zhang H、Ma T、Zhao Y
单位
Department of Breast Oncology II, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital), Shenyang, Liaoning, China.China
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 41383624 · DOI 10.3389/fimmu.2025.1711415