文章：

骨转移：原因、后果和治疗机会

Metastasis to bone: causes, consequences and therapeutic opportunities

原文发布日期：2002-08-01

DOI: 10.1038/nrc867

类型: Review Article

开放获取: 否

要点：

1. Common tumours, such as those of the breast, lung and prostate, frequently metastasize to bone, and in many patients with advanced disease the skeleton is the site of the most significant tumour burden.
2. There are different patterns of bone effects in patients with cancer, ranging from purely or mostly destructive or osteolytic (breast cancer, myeloma), to mostly bone-forming or osteoblastic (prostate cancer).
3. In the case of breast-cancer-causing osteolysis, the main mediator is parathyroid-hormone-related peptide (PTHrP), whereas, in osteoblastic lesions, known mediators include endothelin-1 and platelet-derived growth factor.
4. In osteolytic metastasis, there is a 'vicious cycle' in the bone microenvironment, whereby bi-directional interactions between tumour cells and osteoclasts lead to both osteolysis and tumour growth.
5. The molecular mechanisms that are responsible for this vicious cycle are now being clarified and involve tumour-cell production of PTHrP and bone-derived growth factors that are released as a consequence of increased bone resorption.
6. Bisphosphonates interrupt the vicious cycle and cause not only a reduction in osteolytic bone lesions, but also decrease the tumour burden in bone.
7. More-effective treatments for interruption of the vicious cycle are now being developed, including specifically neutralizing antibodies to PTHrP and more efficacious osteoclast inhibitors.

要点翻译：

1. 常见肿瘤（如乳腺癌、肺癌和前列腺癌）常转移至骨骼，在许多晚期患者中，骨骼是肿瘤负荷最主要的部位。
2. 癌症患者的骨骼效应呈现不同模式，可从纯破坏性或主要呈溶骨性（乳腺癌、骨髓瘤），到主要呈成骨性（前列腺癌）。
3. 在乳腺癌导致的溶骨过程中，主要介质是甲状旁腺激素相关肽（PTHrP）；而在成骨性病变中，已知介质包括内皮素-1和血小板衍生生长因子。
4. 溶骨性转移中存在骨微环境中的"恶性循环"，即肿瘤细胞与破骨细胞之间的双向相互作用导致溶骨和肿瘤生长。
5. 造成这种恶性循环的分子机制目前正在被阐明，涉及肿瘤细胞产生PTHrP以及因骨吸收增加而释放的骨源性生长因子。
6. 双膦酸盐类药物可中断该恶性循环，不仅能减少溶骨性病变，还能降低骨骼中的肿瘤负荷。
7. 目前正在开发更有效的中断该恶性循环的治疗方法，包括特异性中和PTHrP的抗体和更高效的破骨细胞抑制剂。

英文摘要：

The most common human cancers — lung, breast and prostate — have a great avidity for bone, leading to painful and untreatable consequences. What makes some cancers, but not others, metastasize to bone, and how do they alter its physiology? Some of the molecular mechanisms that are responsible have recently been identified, and provide new molecular targets for drug development.

摘要翻译： 

最常见的几种人类癌症——肺癌、乳腺癌和前列腺癌——对骨骼具有极强的亲和力，会导致痛苦且难以治疗的后果。为何某些癌症会转移至骨骼而非其他器官？它们又是如何改变骨骼生理机能的？近期研究已揭示其中部分分子机制，为药物研发提供了新的分子靶点。

原文链接：

Metastasis to bone: causes, consequences and therapeutic opportunities