文章：

软骨肿瘤和骨发育：分子病理学和可能的治疗靶点

Cartilage tumours and bone development: molecular pathology and possible therapeutic targets

原文发布日期：2010-06-10

DOI: 10.1038/nrc2869

类型: Review Article

开放获取: 否

要点：

1. Benign cartilage lesions (enchondromas and osteochondromas) can result from the deregulation of the hedgehog signalling pathway, which is involved in normal bone development.
2. Malignant chondrosarcomas can derive from benign cartilage lesions, with enchondromas developing into central chondrosarcomas and osteochondromas developing into peripheral chondrosarcomas.
3. Peripheral chondrosarcomas have different molecular abnormalities from central chondrosarcomas.
4. The progression from benign to malignant cartilage tumours is not driven by hedgehog signalling, but blocking this pathway may be a potential therapeutic target by inducing tumour cartilage cell differentiation.
5. Genetically modified mice show that p53 and insulin-like growth factor are deregulated when enchondromas progress to central chondrosarcomas.
6. Cytogenetic studies show that cyclin-dependent kinase 4, hypoxia-inducible factor, matrix metalloproteinases, SRC and AKT are activated in central chondrosarcomas, suggesting potential new therapeutic approaches.

要点翻译：

1. 良性软骨病变（内生软骨瘤和骨软骨瘤）可能源于参与正常骨骼发育的hedgehog信号通路失调。
2. 恶性软骨肉瘤可由良性软骨病变发展而来，其中内生软骨瘤可进展为中央型软骨肉瘤，骨软骨瘤可进展为外周型软骨肉瘤。
3. 外周型软骨肉瘤与中央型软骨肉瘤具有不同的分子异常。
4. 从良性到恶性软骨肿瘤的进展并非由hedgehog信号驱动，但阻断该通路可能通过诱导肿瘤软骨细胞分化成为潜在治疗靶点。
5. 基因修饰小鼠模型表明，当内生软骨瘤进展为中央型软骨肉瘤时，p53和胰岛素样生长因子出现失调。
6. 细胞遗传学研究表明，在中央型软骨肉瘤中周期蛋白依赖性激酶4、缺氧诱导因子、基质金属蛋白酶、SRC和AKT均被激活，这提示了潜在的新治疗途径。

英文摘要：

As a group, cartilage tumours are the most common primary bone lesions. They range from benign lesions, such as enchondromas and osteochondromas, to malignant chondrosarcoma. The benign lesions result from the deregulation of the hedgehog signalling pathway, which is involved in normal bone development. These lesions can be the precursors of malignant chondrosarcomas, which are notoriously resistant to conventional chemotherapy and radiotherapy. Cytogenetic studies and mouse models are beginning to identify genes and signalling pathways that have roles in tumour progression, such as hedgehog, p53, insulin-like growth factor, cyclin-dependent kinase 4, hypoxia-inducible factor, matrix metalloproteinases, SRC and AKT, suggesting potential new therapeutic approaches.

摘要翻译： 

软骨肿瘤作为一类疾病，是最常见的原发性骨病变。它们包括从良性病变（如内生软骨瘤和骨软骨瘤）到恶性的软骨肉瘤。良性病变源于参与正常骨骼发育的Hedgehog信号通路的失调。这些病变可能成为恶性软骨肉瘤的前体，而软骨肉瘤对传统的化疗和放疗 notoriously 具有耐药性。细胞遗传学研究和动物模型开始揭示在肿瘤进展中发挥作用的基因和信号通路，例如Hedgehog、p53、胰岛素样生长因子、细胞周期蛋白依赖性激酶4、缺氧诱导因子、基质金属蛋白酶、SRC和AKT，提示了潜在的新治疗途径。

原文链接：

Cartilage tumours and bone development: molecular pathology and possible therapeutic targets