文章：

骨肉瘤的翻译生物学

Translational biology of osteosarcoma

原文发布日期：2014-10-16

DOI: 10.1038/nrc3838

类型: Review Article

开放获取: 否

要点：

1. Osteosarcomas are rare malignancies of bone, affecting primarily children and adolescents. Patients are typically treated with surgery and intensive adjuvant chemotherapy. The 5-year survival rate for recurrent or metastatic osteosarcoma is less than 25%.
2. Bone has a highly specialized microenvironment. Crosstalk between osteoblasts, the cell lineage from which osteosarcoma arises, and monocyte-derived osteoclasts, occurs via signalling molecules that, in many cases, are linked to immune biology.
3. Osteosarcomas are characterized by high levels of genomic instability. Recently, novel mutation patterns have been observed, including chromothripsis and kataegis. Few recurrent, therapeutically targetable mutations have been found.
4. Therapeutic strategies targeting oncogenic kinases have been disappointing, while strategies targeting the osteoclast using denosumab and bisphosphonates are being evaluated.
5. Immune strategies show promise. The immune adjuvant, mifamurtide is the most substantial therapeutic advance in osteosarcoma in the past 10 years.
6. Evidence from preclinical studies suggests that immune checkpoint blockade inhibitors may be useful in the treatment of this disease.

要点翻译：

1. 骨肉瘤是一种罕见的恶性骨肿瘤，主要发生于儿童和青少年。患者通常接受手术及强化辅助化疗治疗。复发或转移性骨肉瘤的5年生存率低于25%。
2. 骨骼拥有高度特化的微环境。成骨细胞（骨肉瘤起源的细胞谱系）与单核细胞衍生的破骨细胞之间通过信号分子进行相互作用，这些信号分子在许多情况下与免疫生物学相关联。
3. 骨肉瘤以高度基因组不稳定性为特征。近年来研究发现新型突变模式，包括染色体碎裂和突变风暴。目前尚未发现具有治疗靶向价值的复发性突变。
4. 针对致癌激酶的治疗策略疗效欠佳，而使用地诺单抗和双膦酸盐靶向破骨细胞的治疗策略正在评估中。
5. 免疫疗法展现出良好前景。免疫佐剂米伐木肽是过去十年间骨肉瘤治疗领域最重大的进展。
6. 临床前研究证据表明，免疫检查点阻断抑制剂可能对该疾病的治疗具有重要价值。

英文摘要：

For the past 30 years, improvements in the survival of patients with osteosarcoma have been mostly incremental. Despite evidence of genomic instability and a high frequency of chromothripsis and kataegis, osteosarcomas carry few recurrent targetable mutations, and trials of targeted agents have been generally disappointing. Bone has a highly specialized immune environment and many immune signalling pathways are important in bone homeostasis. The success of the innate immune stimulant mifamurtide in the adjuvant treatment of non-metastatic osteosarcoma suggests that newer immune-based treatments, such as immune checkpoint inhibitors, may substantially improve disease outcome.

摘要翻译： 

30年来，骨肉瘤患者生存率的提高多为渐进式。尽管存在基因组不稳定性、染色体碎裂（chromothripsis）和 kataegis 高频发生，但骨肉瘤中可靶向的复发突变极少，靶向药物试验总体令人失望。骨具有高度特化的免疫微环境，多条免疫信号通路对骨稳态至关重要。固有免疫激活剂米伐木肽（mifamurtide）用于非转移性骨肉瘤辅助治疗的成功提示，新型免疫治疗（如免疫检查点抑制剂）可能显著改善疾病结局。

原文链接：

Translational biology of osteosarcoma