Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA.
Signal Transduct Target Ther. 2016 Mar 25;1:16001. doi: 10.1038/sigtrans.2016.1. eCollection 2016.
Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents, affecting ~560 young patients in the United States annually. The term OS describes a diverse array of subtypes with varying prognoses, but the majority of tumors are high grade and aggressive. Perhaps because the true etiology of these aggressive tumors remains unknown, advances in OS treatment have reached a discouraging plateau, with only incremental improvements over the past 40 years. Thus, research surrounding the pathogenesis of OS is essential, as it promises to unveil novel therapeutic targets that can attack tumor cells with greater specificity and lower toxicity. Among the candidate molecular targets in OS, the retinoblastoma (RB) pathway demonstrates the highest frequency of inactivation and thus represents a particularly promising avenue for molecular targeted therapy. This review examines the present thinking and practices in OS treatment and specifically highlights the relevance of the RB pathway in osteosarcomagenesis. Through further investigation into RB pathway-related novel therapeutic targets, we believe that a near-term breakthrough in improved OS prognosis is possible.
骨肉瘤(OS)是儿童和青少年中最常见的原发性骨癌,每年影响美国约 560 名年轻患者。OS 这个术语描述了一系列具有不同预后的不同亚型,但大多数肿瘤是高级别和侵袭性的。也许是因为这些侵袭性肿瘤的确切病因仍然未知,OS 治疗方面的进展已经达到了令人沮丧的瓶颈,在过去的 40 年中仅取得了渐进式的改善。因此,围绕 OS 发病机制的研究至关重要,因为它有望揭示新的治疗靶点,可以更特异性和更低毒性地攻击肿瘤细胞。在 OS 中的候选分子靶标中,视网膜母细胞瘤(RB)途径显示出最高的失活频率,因此代表了分子靶向治疗特别有前途的途径。本综述检查了 OS 治疗的现有思维和实践,特别强调了 RB 途径在骨肉瘤发生中的相关性。通过进一步研究 RB 途径相关的新型治疗靶点,我们相信在改善 OS 预后方面近期内可能会取得突破。