School of Pharmacy and Biomedical Science, Curtin University, Bentley 6102, Australia; Curtin Health Innovation Research Institute, Bentley 6102, Australia.
School of Medicine, Curtin University, Bentley 6102, Australia.
Int J Biochem Cell Biol. 2018 Mar;96:63-78. doi: 10.1016/j.biocel.2018.01.003. Epub 2018 Jan 5.
Breast cancer is the most common cancer affecting women worldwide, with bone metastases presenting as the most common site of disease recurrence. Bone metastases secondary to breast cancer negatively impacts patient survival, mobility, and quality of life. Furthermore, the clinical complications of breast cancer bone metastases are associated with significant financial burden to the individual and society. The molecular mechanisms involved in the metastasis, colonisation, and proliferation of breast cancer cells in bone are complex and involve crosstalk between breast cancer cells and the bone microenvironment. The ability of metastatic breast cancer cells to hijack normal biological processes involved in bone remodelling is a key driver of osteolytic and osteoblastic bone lesions. As such, our understanding of how breast cancer cells manipulate normal bone remodelling pathways is essential for the development of new therapeutic agents to improve patient outcomes. In this review, we discuss bone remodelling under normal physiological conditions and explore key pathways dysregulated in breast cancer metastasis to bone. We provide an overview of systemic therapies currently recommended for the treatment of breast cancer bone metastases and highlight emerging therapeutic targets.
乳腺癌是全球范围内最常见的女性癌症,骨转移是最常见的疾病复发部位。乳腺癌骨转移会降低患者的生存率、活动能力和生活质量。此外,乳腺癌骨转移的临床并发症会给个人和社会带来巨大的经济负担。乳腺癌细胞在骨中转移、定植和增殖的分子机制非常复杂,涉及乳腺癌细胞与骨微环境之间的串扰。转移性乳腺癌细胞劫持涉及骨重塑的正常生物学过程的能力是溶骨性和成骨性骨病变的关键驱动因素。因此,我们对乳腺癌细胞如何操纵正常骨重塑途径的理解对于开发改善患者预后的新治疗药物至关重要。在这篇综述中,我们讨论了正常生理条件下的骨重塑,并探讨了乳腺癌骨转移中失调的关键途径。我们概述了目前推荐用于治疗乳腺癌骨转移的系统疗法,并强调了新的治疗靶点。