INSERM, UMR1033, F-69008 Lyon, France.
Breast Cancer Res. 2011 Apr 6;13(2):207. doi: 10.1186/bcr2835.
Breast cancer is prone to metastasize to bone. Once metastatic cells are in the bone marrow, they do not, on their own, destroy bone. Instead, they alter the functions of bone-resorbing (osteoclasts) and bone-forming cells (osteoblasts), resulting in skeletal complications that cause pathological fractures and pain. In this review, we describe promising molecular bone-targeted therapies that have arisen from recent advances in our understanding of the pathogenesis of breast cancer bone metastases. These therapies target osteoclasts (receptor activator of nuclear factor kB ligand, integrin αvβ3, c-Src, cathepsin K), osteoblasts (dickkopf-1, activin A, endothelin A) and the bone marrow microenvironment (transforming growth factor β, bone morphogenetic proteins, chemokine CXCL-12 and its receptor CXCR4). The clinical exploitation of these bone-targeted agents will provide oncologists with novel therapeutic strategies for the treatment of skeletal lesions in breast cancer.
乳腺癌易转移至骨骼。一旦转移细胞进入骨髓，它们并不会自行破坏骨骼。相反，它们改变了破骨细胞（osteoclasts）和造骨细胞（osteoblasts）的功能，导致骨骼并发症，引起病理性骨折和疼痛。在这篇综述中，我们描述了一些有前景的分子靶向骨治疗方法，这些方法源自我们对乳腺癌骨转移发病机制的理解的最新进展。这些治疗方法针对破骨细胞（核因子 κB 配体受体激活剂、整合素 αvβ3、c-Src、组织蛋白酶 K）、成骨细胞（Dickkopf-1、激活素 A、内皮素 A）和骨髓微环境（转化生长因子 β、骨形态发生蛋白、趋化因子 CXCL-12 和其受体 CXCR4）。这些骨靶向药物的临床应用将为肿瘤学家提供治疗乳腺癌骨骼病变的新的治疗策略。
