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骨肉瘤中的NOTCH信号通路

NOTCH Signaling in Osteosarcoma.

作者信息

Zhang Zhenhao, Wu Wei, Shao Zengwu

机构信息

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Curr Issues Mol Biol. 2023 Mar 8;45(3):2266-2283. doi: 10.3390/cimb45030146.

Abstract

The combination of neoadjuvant chemotherapy and surgery has been promoted for the treatment of osteosarcoma; however, the local recurrence and lung metastasis rates remain high. Therefore, it is crucial to explore new therapeutic targets and strategies that are more effective. The NOTCH pathway is not only involved in normal embryonic development but also plays an important role in the development of cancers. The expression level and signaling functional status of the NOTCH pathway vary in different histological types of cancer as well as in the same type of cancer from different patients, reflecting the distinct roles of the Notch pathway in tumorigenesis. Studies have reported abnormal activation of the NOTCH signaling pathway in most clinical specimens of osteosarcoma, which is closely related to a poor prognosis. Similarly, studies have reported that NOTCH signaling affected the biological behavior of osteosarcoma through various molecular mechanisms. NOTCH-targeted therapy has shown potential for the treatment of osteosarcoma in clinical research. After the introduction of the composition and biological functions of the NOTCH signaling pathway, the review paper discussed the clinical significance of dysfunction in osteosarcoma. Then the paper reviewed the recent relevant research progress made both in the cell lines and in the animal models of osteosarcoma. Finally, the paper explored the potential of the clinical application of NOTCH-targeted therapy for the treatment of osteosarcoma.

摘要

新辅助化疗与手术相结合已被推广用于骨肉瘤的治疗;然而,局部复发率和肺转移率仍然很高。因此,探索更有效的新治疗靶点和策略至关重要。NOTCH信号通路不仅参与正常胚胎发育,而且在癌症发生发展中也发挥着重要作用。NOTCH信号通路的表达水平和信号功能状态在不同组织学类型的癌症以及不同患者的同一类型癌症中有所不同,这反映了Notch信号通路在肿瘤发生中的不同作用。研究报道,在大多数骨肉瘤临床标本中NOTCH信号通路存在异常激活,这与预后不良密切相关。同样,研究报道NOTCH信号通过多种分子机制影响骨肉瘤的生物学行为。在临床研究中,NOTCH靶向治疗已显示出治疗骨肉瘤的潜力。在介绍NOTCH信号通路的组成和生物学功能后,该综述论文讨论了骨肉瘤中功能障碍的临床意义。然后,该论文综述了骨肉瘤细胞系和动物模型中最近取得的相关研究进展。最后,该论文探讨了NOTCH靶向治疗在骨肉瘤临床应用中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/10047431/21123b539efc/cimb-45-00146-g001.jpg

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