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MET/HGF 通路在多发性骨髓瘤中的作用:从诊断到靶向治疗?

MET/HGF pathway in multiple myeloma: from diagnosis to targeted therapy?

机构信息

Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.

出版信息

Expert Rev Mol Diagn. 2015;15(7):881-93. doi: 10.1586/14737159.2015.1046436. Epub 2015 May 12.

Abstract

The interaction between neoplastic cells and the microenvironment is critical in several cancers and plays a central role in multiple myeloma. Microenvironmental stimuli support plasma cell proliferation, survival, motility and can determine drug resistance. The network between plasma cells and surrounding cells is also responsible for increasing angiogenesis, unbalancing bone formation and bony lesions. The MET/HGF pathway is a key player in this interaction and has been found to be abnormally active in both malignant plasma cells and surrounding cells. Patients with abnormal MET and/or HGF levels usually have a poor outcome even when treated with novel drugs. This review addresses the role of MET/HGF in the pathogenesis of myeloma and describes the role of MET/HGF signaling as a prognostic factor. The different techniques to detect MET/HGF abnormalities are examined and a description of compounds targeting MET/HGF is also provided.

摘要

肿瘤细胞与微环境的相互作用在多种癌症中至关重要,并且在多发性骨髓瘤中起着核心作用。微环境刺激支持浆细胞增殖、存活、迁移,并可决定药物耐药性。浆细胞与周围细胞之间的网络也负责增加血管生成、打破骨形成和骨病变的平衡。MET/HGF 通路是这种相互作用的关键参与者,已发现异常活跃于恶性浆细胞和周围细胞中。即使使用新型药物治疗,MET 和/或 HGF 水平异常的患者通常预后不良。这篇综述探讨了 MET/HGF 在骨髓瘤发病机制中的作用,并描述了 MET/HGF 信号作为预后因素的作用。本文还检查了检测 MET/HGF 异常的不同技术,并提供了针对 MET/HGF 的化合物描述。

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