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小细胞肺癌中的MET抑制剂:从实验室到临床

MET Inhibitors in Small Cell Lung Cancer: From the Bench to the Bedside.

作者信息

Hardy-Werbin Max, Del Rey-Vergara Raúl, Galindo-Campos Miguel Alejandro, Moliner Laura, Arriola Edurne

机构信息

Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), 08003 Barcelona, Spain.

Medical Oncology Department, Hospital del Mar-CIBERONC, 08003 Barcelona, Spain.

出版信息

Cancers (Basel). 2019 Sep 20;11(10):1404. doi: 10.3390/cancers11101404.

Abstract

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. The different systemic treatment approaches attempted in the last 35 years have not improved overall survival in the advanced stage. Targeted therapies assessed in clinical trials have failed to show efficacy against SCLC. Within the potentially interesting targets, the hepatocyte growth factor (HGF)/mesenchymal-epithelial transition (MET) pathway activation is associated with worse survival and chemoresistance in SCLC. Preclinical data suggest that the inhibition of the MET pathway can revert chemoresistance and prevent tumor growth. Recently, immunotherapy has shown modest but relevant activity in SCLC. Interestingly, MET modulation seems to be involved in increasing the efficacy of standard checkpoint inhibitors. Here, we review the preclinical and clinical data of MET inhibition in SCLC, and the role of this pathway in the immune response.

摘要

小细胞肺癌(SCLC)是最具侵袭性的肺癌类型。在过去35年中尝试的不同全身治疗方法并未改善晚期患者的总生存期。在临床试验中评估的靶向治疗未能显示出对SCLC的疗效。在潜在的有意义的靶点中,肝细胞生长因子(HGF)/间充质-上皮转化(MET)途径激活与SCLC患者较差的生存率和化疗耐药性相关。临床前数据表明,抑制MET途径可逆转化疗耐药性并阻止肿瘤生长。最近,免疫疗法在SCLC中显示出适度但相关的活性。有趣的是,MET调节似乎参与提高标准检查点抑制剂的疗效。在此,我们综述了SCLC中MET抑制的临床前和临床数据,以及该途径在免疫反应中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79f1/6827355/db4defdadd34/cancers-11-01404-g001.jpg

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