Dass Crispin R, Ek Eugene T H, Choong Peter F M
Department of Orthopaedics and Surgery, University of Melbourne, St Vincent's Hospital, Melbourne, Australia.
Curr Cancer Drug Targets. 2008 Dec;8(8):683-90. doi: 10.2174/156800908786733487.
Osteosarcoma (OS) is a disease that afflicts teenagers and adolescents in the prime of their lives. In spite of surgery and therapies currently used, there is a 1/3 chance of relapse. As for other cancers, current research is largely devoted to elucidating the molecular basis of the disease, with the anticipation that such research will lead to discovery and development of biological therapies. The major advantage of utilising such therapy is the relative lack of toxicity to normal tissues. One such enterprising candidate molecule, pigment epithelium-derived factor (PEDF), has recently been implicated to be involved in control of OS in orthotopic spontaneously metastasising models of the disease, whether administered as recombinant protein, overexpressed or administered as short peptides derived from the parent molecule. Expression of PEDF is inversely proportional to expression of vascular endothelial growth factor (VEGF) at the growth plate cartilage layer of growing bone in both mice and man. PEDF, originally discovered for its potent antiangiogenic activity, is now established as an anticancer factor with multiple mechanisms at its disposal for tumour inhibition. Current efforts are devoted to develop drug delivery systems, such as controlled release nanoparticles, that can be used to progress this potential drug candidate closer towards clinical trials for OS.
骨肉瘤(OS)是一种困扰青少年和处于生命黄金期的年轻人的疾病。尽管目前采用了手术和治疗方法,但仍有三分之一的复发几率。与其他癌症一样,当前的研究主要致力于阐明该疾病的分子基础,期望此类研究能引领生物疗法的发现与开发。利用此类疗法的主要优势在于对正常组织的毒性相对较低。一种这样具有开拓性的候选分子,即色素上皮衍生因子(PEDF),最近在该疾病的原位自发转移模型中被发现与骨肉瘤的控制有关,无论是作为重组蛋白给药、过表达还是作为源自母体分子的短肽给药。在小鼠和人类生长骨骼的生长板软骨层,PEDF的表达与血管内皮生长因子(VEGF)的表达呈负相关。PEDF最初因其强大的抗血管生成活性而被发现,现在已被确立为一种抗癌因子,具备多种抑制肿瘤的机制。目前的工作致力于开发药物递送系统,如控释纳米颗粒,可用于推动这种潜在的候选药物更接近骨肉瘤的临床试验。