Université de Nantes, INSERM, UMR1238, Phy-OS, Sarcomes Osseux et Remodelage des Tissus Calcifiés, 44035 Nantes, France.
Int J Mol Sci. 2019 Jul 31;20(15):3751. doi: 10.3390/ijms20153751.
Osteosarcoma and Ewing sarcoma are the most common malignant primary bone tumors mainly occurring in children, adolescents and young adults. Current standard therapy includes multidrug chemotherapy and/or radiation specifically for Ewing sarcoma, associated with tumor resection. However, patient survival has not evolved for the past decade and remains closely related to the response of tumor cells to chemotherapy, reaching around 75% at 5 years for patients with localized forms of osteosarcoma or Ewing sarcoma but less than 30% in metastatic diseases and patients resistant to initial chemotherapy. Despite Ewing sarcoma being characterized by specific gene fusions resulting in oncogenic transcription factors, currently, no targeted therapy could be implemented. It seems even more difficult to develop a targeted therapeutic strategy in osteosarcoma which is characterized by high complexity and heterogeneity in genomic alterations. Nevertheless, the common point between these different bone tumors is their ability to deregulate bone homeostasis and remodeling and divert them to their benefit. Therefore, targeting different actors of the bone tumor microenvironment has been hypothesized to develop new therapeutic strategies. In this context, it is well known that the Wnt/β-catenin signaling pathway plays a key role in cancer development, including osteosarcoma and Ewing sarcoma as well as in bone remodeling. Moreover, recent studies highlight the implication of the Wnt/β-catenin pathway in angiogenesis and immuno-surveillance, two key mechanisms involved in metastatic dissemination. This review focuses on the role played by this signaling pathway in the development of primary bone tumors and the modulation of their specific microenvironment.
骨肉瘤和尤文肉瘤是最常见的恶性原发性骨肿瘤，主要发生在儿童、青少年和年轻成人中。目前的标准治疗包括多药化疗和/或放疗，特别是针对尤文肉瘤，同时结合肿瘤切除术。然而，过去十年患者的生存率并没有提高，仍然与肿瘤细胞对化疗的反应密切相关，局部骨肉瘤或尤文肉瘤患者的 5 年生存率约为 75%，但转移性疾病和对初始化疗耐药的患者的生存率不到 30%。尽管尤文肉瘤的特征是特定基因融合导致致癌转录因子，但目前尚无靶向治疗方法。在骨肉瘤中开发靶向治疗策略似乎更加困难，因为骨肉瘤在基因组改变方面具有高度复杂性和异质性。然而，这些不同的骨肿瘤之间的共同点是它们能够使骨内稳态和重塑失调，并从中受益。因此，靶向肿瘤微环境的不同因素已被假设为开发新的治疗策略。在这种情况下，众所周知，Wnt/β-catenin 信号通路在癌症发展中发挥着关键作用，包括骨肉瘤和尤文肉瘤以及骨重塑。此外，最近的研究强调了 Wnt/β-catenin 途径在血管生成和免疫监视中的作用，这是转移扩散中涉及的两个关键机制。这篇综述重点介绍了该信号通路在原发性骨肿瘤发展中的作用及其对特定微环境的调节。
