Department of Hematology/Oncology, University of Alabama at Birmingham , Birmingham , AL , USA.
Dana Farber Cancer Institute and Harvard Medical School , Boston , MA , USA.
Expert Opin Investig Drugs. 2019 Oct;28(10):851-860. doi: 10.1080/13543784.2019.1673366. Epub 2019 Oct 3.
: Renal cell carcinoma (RCC) consists of distinct clinical and biologic entities, with an urgent need for novel therapies targeting histology-specific molecular drivers of cancer growth. The MET pathway is now being targeted by multiple novel agents in clinical development. This review highlights the upcoming role of MET inhibition in the treatment of RCC. : The HGF-MET axis is now recognized as playing a vital role in the growth of papillary histology and in driving VEGF inhibitor resistance. The heterogeneity of MET alterations influences sensitivity to MET inhibition and we need predictive biomarkers for improving patient selection. In this review, we highlight the role of the MET pathway in both clear cell and non-clear cell RCC and provide a comprehensive review of preclinical and early clinical data on multiple drugs targeting the MET pathway. : MET alterations can act as primary or secondary drivers of tumor growth in RCC and represents a viable therapeutic target. Combination strategies of VEGF and MET inhibitors could lead to sustained and deep responses even in non-MET driven RCC by inhibiting pathways of VEGF resistance. Addition of checkpoint inhibitors to MET inhibition has also demonstrated promising signs of early efficacy.
: 肾细胞癌 (RCC) 由不同的临床和生物学实体组成，迫切需要针对癌症生长的组织特异性分子驱动因素的新型治疗方法。MET 通路目前正被多种处于临床开发阶段的新型药物靶向。本综述强调了 MET 抑制在 RCC 治疗中的作用。: HGF-MET 轴现在被认为在乳头状组织学的生长和驱动 VEGF 抑制剂耐药性中起着至关重要的作用。MET 改变的异质性影响对 MET 抑制的敏感性，我们需要预测性生物标志物来改善患者选择。在本综述中，我们强调了 MET 通路在透明细胞和非透明细胞 RCC 中的作用，并对靶向 MET 通路的多种药物的临床前和早期临床数据进行了全面综述。: MET 改变可作为 RCC 肿瘤生长的主要或次要驱动因素，是一个可行的治疗靶点。VEGF 和 MET 抑制剂的联合策略可通过抑制 VEGF 耐药途径，即使在非 MET 驱动的 RCC 中也能导致持续和深度的反应。将检查点抑制剂添加到 MET 抑制中也显示出早期疗效的有希望迹象。
