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理解和靶向实体瘤中的MET信号传导——我们做到了吗?

Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?

作者信息

Ariyawutyakorn Witthawat, Saichaemchan Siriwimon, Varella-Garcia Marileila

机构信息

1. Faculty of Medicine, Chiang Mai University, 110 Intavarorod Rd., Muang, Chiang Mai, Thailand 50200.; 3. Department of Medicine, University of Colorado, Anschutz Medical Campus, 12801 East 17th Ave, RC1 South, L18-8118, Mail Stop 8117, Aurora, Colorado, USA 80045.

2. Division of Oncology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, 315 Phayathai Rd., Ratchathewi, Bangkok, Thailand 10400.; 3. Department of Medicine, University of Colorado, Anschutz Medical Campus, 12801 East 17th Ave, RC1 South, L18-8118, Mail Stop 8117, Aurora, Colorado, USA 80045.

出版信息

J Cancer. 2016 Mar 20;7(6):633-49. doi: 10.7150/jca.12663. eCollection 2016.

Abstract

The MET signaling pathway plays an important role in normal physiology and its deregulation has proved critical for development of numerous solid tumors. Different technologies have been used to investigate the genomic and proteomic status of MET in cancer patients and its association with disease prognosis. Moreover, with the development of targeted therapeutic drugs, there is an urgent need to identify potential biomarkers for selection of patients who are more likely to derive benefit from these agents. Unfortunately, the variety of technical platforms and analysis criteria for diagnosis has brought confusion to the field and a lack of agreement in the evaluation of MET status as a prognostic or predictive marker for targeted therapy agents. We review the molecular mechanisms involved in the deregulation of the MET signaling pathway in solid tumors, the different technologies used for diagnosis, and the main factors that affect the outcome, emphasizing the urge for completing analytical and clinical validation of these tests. We also review the current clinical studies with MET targeted agents, which mostly focus on lung cancer.

摘要

MET信号通路在正常生理过程中发挥着重要作用,其失调已被证明对多种实体瘤的发展至关重要。已采用不同技术来研究癌症患者中MET的基因组和蛋白质组状态及其与疾病预后的关联。此外,随着靶向治疗药物的发展,迫切需要识别潜在的生物标志物,以选择更有可能从这些药物中获益的患者。不幸的是,各种技术平台和诊断分析标准给该领域带来了混乱,在将MET状态评估为靶向治疗药物的预后或预测标志物方面缺乏共识。我们综述了实体瘤中MET信号通路失调所涉及的分子机制、用于诊断的不同技术以及影响结果的主要因素,强调了完成这些检测的分析和临床验证的紧迫性。我们还综述了目前使用MET靶向药物的临床研究,这些研究大多聚焦于肺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b07/4829549/684d5bfec888/jcav07p0633g001.jpg

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