Department of Medicine, Goodman Cancer Centre, McGill University, QC H3A 1A3, Canada.
Future Oncol. 2010 Jan;6(1):55-74. doi: 10.2217/fon.09.138.
In the past decade, our understanding of the molecular mechanisms that underlie breast cancer pathology and progression has dramatically improved. Using this knowledge, we have identified additional targets and developed novel therapeutic interventions in breast cancer. Together, these translational research efforts are helping to usher us into an age of personalized cancer therapy. Metastasis to bone is a common and devastating consequence of breast cancer. Bisphosphonates, which represent the current gold standard in bone metastasis therapies, are being improved with newer and more efficacious generations of these compounds being developed. Breast cancer growth in the bone requires activation of various signaling pathways in both cancer cells and stromal cells, including those that are stimulated by TGF-beta and RANKL, and mediated through the Src tyrosine kinase. Bone cells and cancer cells alike express promising targets for therapeutic intervention, including Cathepsin K, CXCR4 and GPNMB. In this article we discuss the molecular mechanisms behind these pro-metastatic molecules and review the most recent findings in the clinical development of their associated targeted therapies.
在过去的十年中，我们对乳腺癌病理学和进展的分子机制的理解有了显著的提高。利用这些知识，我们已经确定了其他靶点，并开发了新的乳腺癌治疗干预措施。这些转化研究工作共同帮助我们迈入了个性化癌症治疗的时代。骨转移是乳腺癌的常见且破坏性后果。双膦酸盐是目前骨转移治疗的金标准，正在通过开发更新、更有效的此类化合物进行改进。乳腺癌在骨骼中的生长需要激活癌细胞和基质细胞中的各种信号通路，包括那些由 TGF-β和 RANKL 刺激的通路，并通过Src 酪氨酸激酶介导。骨细胞和癌细胞都表达有希望的治疗干预靶点，包括组织蛋白酶 K、CXCR4 和 GPNMB。本文讨论了这些促转移分子背后的分子机制，并回顾了其相关靶向治疗的临床开发的最新发现。
