a Department of Histology and Cell Biology , Matsumoto Dental University , Shiojiri , Nagano , Japan.
Expert Opin Investig Drugs. 2016;25(3):319-34. doi: 10.1517/13543784.2016.1142972. Epub 2016 Feb 6.
Bone is one of the preferential organs affected in patients with metastatic cancers. Bone metastases contribute substantially to morbidity and mortality in cancer patients, especially for those with breast and prostate cancer. Bisphosphonates and denosumab, potent inhibitors of osteoclastic bone resorption, are the current standard of care for bone metastases; however, their effects are palliative. Recent preclinical studies have revealed a variety of potential targets for the development of novel therapeutic agents. Some of these are currently being evaluated in clinical trials.
This paper reviews the preclinical and early clinical development of molecularly targeted agents for the treatment of bone metastases. The agents are categorized according to their targets, osteoclasts, osteoblasts, metastatic cancer cells, and the bone microenvironment.
Recent advances in our understanding of the molecular and cellular mechanisms of bone metastases have led to the development of novel therapeutic options. Although most of their effects have yet to be proved in clinical studies, it is the author's belief that they will contribute significantly to improving the treatment outcome of patients with bone metastases in the near future.
骨骼是转移性癌症患者中优先受累的器官之一。骨转移极大地影响了癌症患者的发病率和死亡率，特别是乳腺癌和前列腺癌患者。双膦酸盐和地舒单抗是骨转移的标准治疗药物，它们是强效的破骨细胞骨吸收抑制剂；然而，它们的作用只是姑息性的。最近的临床前研究揭示了许多开发新型治疗药物的潜在靶点。其中一些目前正在临床试验中进行评估。
本文综述了用于治疗骨转移的分子靶向药物的临床前和早期临床开发。根据作用靶点将这些药物进行分类，包括破骨细胞、成骨细胞、转移性癌细胞和骨微环境。
我们对骨转移分子和细胞机制的理解的最新进展，导致了新型治疗选择的出现。尽管它们的大多数作用尚未在临床研究中得到证实，但作者相信，它们将在不久的将来显著改善骨转移患者的治疗效果。
