Wu Ping, Morgan Gareth J
Section of Haemato-Oncology, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
Cancer Microenviron. 2011 Dec;4(3):299-311. doi: 10.1007/s12307-011-0079-2. Epub 2011 Aug 11.
Myeloma bone disease (BD) not only impairs quality of life, but is also associated with impaired survival. Studies of the biology underlying BD support the notion that the increased osteoclastogenesis and suppressed osteoblastogenesis, is both a consequence and a necessity for tumour growth and clonal expansion. Survival and expansion of the myeloma clone is dependent on its interactions with bone elements, thus targeting these interactions should have antimyeloma activities. Indeed both experimental and clinical findings indicate that bone-targeted therapies not only improve BD, but also create an inhospitable environment for myeloma cell growth and survival, favouring improved clinical outcome. This review summarizes recent progress in our understandings of the biology of myeloma BD, highlighting the role of osteoclasts and osteoblasts in this process and how they can be targeted therapeutically. Unravelling the mechanisms underlying myeloma-bone interactions will facilitate the development of novel therapeutic agents to treat BD, which as a consequence are likely to improve the clinical outcome of myeloma patients.
骨髓瘤骨病(BD)不仅会损害生活质量,还与生存率降低有关。对BD潜在生物学机制的研究支持这样一种观点,即破骨细胞生成增加和成骨细胞生成受抑制,既是肿瘤生长和克隆性扩增的结果,也是其必要条件。骨髓瘤克隆的存活和扩增依赖于其与骨成分的相互作用,因此针对这些相互作用应具有抗骨髓瘤活性。事实上,实验和临床研究结果均表明,以骨为靶点的治疗不仅能改善BD,还能为骨髓瘤细胞的生长和存活创造不利环境,从而有利于改善临床结局。本综述总结了我们对骨髓瘤BD生物学机制理解的最新进展,强调了破骨细胞和成骨细胞在这一过程中的作用以及如何对其进行靶向治疗。阐明骨髓瘤与骨相互作用的潜在机制将有助于开发治疗BD的新型治疗药物,从而可能改善骨髓瘤患者的临床结局。