Heymann Marie-Françoise, Brown Hannah K, Heymann Dominique
a Department of Oncology and Metabolism, Medical School , University of Sheffield , Sheffield , UK.
b INSERM, UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Equipe Ligue 2012, Faculty of Medicine , University of Nantes , Nantes , France.
Expert Opin Investig Drugs. 2016 Nov;25(11):1265-1280. doi: 10.1080/13543784.2016.1237503. Epub 2016 Sep 25.
Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma.
骨肉瘤是儿童和青少年中主要的原发性恶性骨肿瘤。传统治疗方法基于诊断和切除手术，并结合多药化疗。这是20世纪70年代确立的方案。不幸的是，这种治疗方法已达到疗效平台期，在过去四十年中患者生存率并未提高。因此需要新的治疗方法来改善骨肉瘤患者的预后。涵盖领域：通过现有数据库和已发表的科学文献，本综述概述了目前处于骨肉瘤治疗早期临床开发阶段的药物。对于每种药物，简要介绍了支持其开发的相关科学数据。专家观点：鉴于骨肉瘤亚型的异质性和多种治疗反应，多药靶向方法即将出现。微环境在该疾病中所起的关键作用增加了治疗靶点（如巨噬细胞或破骨细胞）的数量，以及控制细胞增殖或细胞死亡的主要蛋白质的数量。正在进行的I/II期试验是重要步骤，不仅用于确定具有更高安全性和疗效的新疗法，还用于更好地界定微环境在骨肉瘤发病机制中所起的作用。
