Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancer Control. 2012 Apr;19(2):92-101. doi: 10.1177/107327481201900203.
Bone metastases cause morbidity and mortality in multiple malignancies. In addition to portending a dire prognosis, bone metastases cause bone pain, fractures, hypercalcemia, spinal cord compression, and other nerve compression syndromes. Improved understanding of the mechanisms that predispose tumor metastases to bone is needed to improve patients' therapeutic options, maintain their quality of life, and improve their survival.
This review discusses selected preclinical and clinical data regarding bone metastasis development and cytokine/molecular interactions predisposing to bone metastases formation. Potential interventions for reducing bone metastases are also described.
Biologic mechanisms resulting in metastases of tumor cells to bone are being studied. Among these are the RANKL pathway, osteoclast activation via cytokines (produced by tumor cell and cells in the bone microenvironment), interactions with transient and stromal cells in the bone microenvironment, and molecules such as PTHrP and endothelin-1. These molecules offer important opportunities for targeted interventions to decrease bone metastases-associated morbidity.
Knowledge of the pathophysiology of bone and cancer is developing rapidly. Relationships among cancer cells, bone-derived cells, and cytokines provide opportunities for the development of new interventions. Therapy targeting osteoclast/osteoblast interactions has proven benefit for patients with bone metastases.
骨转移可导致多种恶性肿瘤的发病率和死亡率。除了预示着预后不良外，骨转移还会导致骨痛、骨折、高钙血症、脊髓压迫和其他神经压迫综合征。为了改善患者的治疗选择、维持其生活质量并提高其生存率，需要更好地了解促使肿瘤转移至骨骼的机制。
本文讨论了关于骨转移发展和促使骨转移形成的细胞因子/分子相互作用的选定临床前和临床数据。还描述了潜在的减少骨转移的干预措施。
正在研究导致肿瘤细胞转移至骨骼的生物学机制。其中包括 RANKL 通路、通过细胞因子（由肿瘤细胞和骨骼微环境中的细胞产生）激活破骨细胞、与骨骼微环境中的瞬时细胞和基质细胞的相互作用，以及 PTHrP 和内皮素-1 等分子。这些分子为减少与骨转移相关的发病率提供了重要的靶向干预机会。
骨骼和癌症的病理生理学知识正在迅速发展。癌细胞、骨骼来源细胞和细胞因子之间的关系为新的干预措施的发展提供了机会。针对破骨细胞/成骨细胞相互作用的治疗已被证明对有骨转移的患者有益。
