Hayashi Shinichi, Hanamura Toru
Department of Molecular and Functional Dynamics, Tohoku University Graduate School of Medicine.
Clin Calcium. 2011 Mar;21(3):389-96.
Bone, as well as liver and lungs, is one of the most preferential metastatic targets for solid cancers including breast, prostate, and lung cancers. Control of the bone metastasis is clinically important ; because they are frequently associated with bone pain and pathological fracture which greatly diminish the quality of life for patients. Interaction between cancer cells and microenvironment of metastatic site play an important role for establishment of cancer metastasis. The understanding of their mechanisms has been improved in recent years, and they will be new therapeutic strategies to cure the bone metastasis. Bisphosphonates has been clinically used for the bone metastasis. In addition, RANKL-RANK targeted drugs and cathepsin K inhibitors are also expected to be fruitful drugs for the bone metastasis. In this review paper, we summarize the molecular mechanism of these drugs, especially with regarding to the breast cancer bone metastasis. Furthermore, we touch upon the ubiquitin ligase CHIP which recently found as a master gene in the progression and metastasis of breast cancer.
骨骼以及肝脏和肺脏，是包括乳腺癌、前列腺癌和肺癌在内的实体癌最优先转移的靶器官之一。控制骨转移在临床上很重要，因为它们常伴有骨痛和病理性骨折，这会大大降低患者的生活质量。癌细胞与转移部位微环境之间的相互作用在癌症转移的形成中起着重要作用。近年来，对其机制的认识有所提高，它们将成为治疗骨转移的新策略。双膦酸盐已在临床上用于治疗骨转移。此外，RANKL-RANK靶向药物和组织蛋白酶K抑制剂也有望成为治疗骨转移的有效药物。在这篇综述文章中，我们总结了这些药物的分子机制，特别是关于乳腺癌骨转移的机制。此外，我们还提到了泛素连接酶CHIP，它最近被发现是乳腺癌进展和转移中的一个主控基因。
