《生命科学》 2026, 38(7): 1208-1220

乳腺癌骨转移发生机制和靶向治疗的研究进展

张瑞萍¹ , 甘晓霖² , 李彦姝^3,*

¹锦州医科大学第三临床医学院，锦州 121001 ²锦州医科大学体育与运动康复学院，锦州 121001 ³中国医科大学生命科学学院分子细胞生物学教研室，教育部医学细胞生物学重点实验室暨卫健委细胞生物学重点实验室，沈阳 110122

摘　要：

乳腺癌（breast cancer，BC）是全球女性中最常见的恶性肿瘤，其远处转移以骨转移最为常见。本文系统阐 述了BC骨转移的五个阶段，包括转移前生态位的建立、乳腺癌细胞（breast cancer cells，BCCs）血行播散、BCCs在骨 组织中的定植、BCCs的休眠与再激活以及骨转移灶的形成，为临床治疗提供理论依据。同时，本文综述了BC骨转移 的经典靶点，如细胞周期蛋白依赖性激酶4/6（CDK4/6）、雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2 （HER2），以及近年来的潜在治疗靶点，包括酪氨酸激酶SRC、白细胞介素-1β（IL-1β）、C-X-C趋化因子受体4 （CXCR4）等，并介绍了相关最新临床研究进展。综上，本文旨在为克服现有靶向药物在BC骨转移治疗中存在的耐 药性和副作用提供研究思路与方向。

通讯作者：李彦姝 , Email:ysli@cmu.edu.cn

Progress in mechanism and targeted therapy of bone metastases in breast cancer

ZHANG Rui-Ping¹ , GAN Xiao-Lin² , LI Yan-Shu^3,*

¹The Third Clinical Medical College, Jinzhou Medical University, Jinzhou 121001, China ²School of Physical Education and Sports Rehabilitation, Jinzhou Medical University, Jinzhou 121001, China ³Department of Cell Biology, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, Shenyang 110122, China

Abstract:

Breast cancer (BC) is the most prevalent malignancy among women worldwide, with bone representing the most frequent site of distant metastasis. This review outlines the mechanisms underlying BC bone metastasis across five stages: establishment of the pre-metastatic niche, hematogenous dissemination of breast cancer cells (BCCs), colonization within the bone microenvironment, dormancy and reactivation of BCCs, and the formation of overt bone metastatic lesions, thereby providing a theoretical framework for therapeutic development. In addition, we summarize current therapeutic strategies targeting classical molecules such as cyclin-dependent kinase 4/6 (CDK4/6), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and highlight recent clinical advances in emerging targets including tyrosine kinase SRC, interleukin-1β (IL-1β), and C-X-C chemokine receptor type 4 (CXCR4). Collectively, these insights may guide the development of novel therapeutic strategies aimed at overcoming drug resistance and minimizing adverse effects associated with existing targeted therapies for BC bone metastasis.

Communication Author：LI Yan-Shu , Email:ysli@cmu.edu.cn