Chirgwin John M, Guise Theresa A
The Aurbach Laboratory, Division of Endocrinology, Department of Medicine, University of Virginia, Charlottesville, Virginia 22903, USA.
J Cell Biochem. 2007 Dec 15;102(6):1333-42. doi: 10.1002/jcb.21556.
Several common cancers often metastasize to the skeleton in advanced disease. Bone metastases are incurable and cause protracted, severe symptoms. Growth of tumor in bone is driven by a vicious cycle: tumor-secreted factors stimulate bone cells, which in turn release growth factors and cytokines. The bone-derived factors fuel the vicious cycle by acting back on the tumor cells. The vicious cycle offers novel targets for the treatment of advanced cancers. Treatments can inhibit bone cells (osteoclasts and osteoblasts) that are stimulated by tumor-secreted factors. Drugs can also inhibit tumor responses to factors enriched in the bone microenvironment, such as transforming growth factor-beta. Animal models show that these approaches, especially combination treatments, can reduce tumor burden. The results suggest a novel paradigm in which tumor growth can be effectively inhibited by drugs that target cells in the bone microenvironment and not the tumor cells themselves.
几种常见癌症在疾病晚期常转移至骨骼。骨转移无法治愈，并会引发长期、严重的症状。骨中肿瘤的生长由一个恶性循环驱动：肿瘤分泌的因子刺激骨细胞，骨细胞进而释放生长因子和细胞因子。骨源性因子通过作用于肿瘤细胞而加剧这个恶性循环。这个恶性循环为晚期癌症的治疗提供了新的靶点。治疗方法可以抑制受肿瘤分泌因子刺激的骨细胞（破骨细胞和成骨细胞）。药物还可以抑制肿瘤对骨微环境中富集的因子（如转化生长因子-β）的反应。动物模型表明，这些方法，尤其是联合治疗，可以减轻肿瘤负担。结果提示了一种新的模式，即通过靶向骨微环境中的细胞而非肿瘤细胞本身的药物，可以有效抑制肿瘤生长。
