a Department of Pharmaceutical Sciences, College of Pharmacy , The University of Findlay , Findlay , OH , USA.
Expert Opin Investig Drugs. 2019 Feb;28(2):121-130. doi: 10.1080/13543784.2019.1559296. Epub 2018 Dec 21.
The incidence of renal cell carcinoma (RCC) has increased in recent years and, unfortunately, many patients initially present with metastatic disease. When surgery is not an option, treatment involves administration of targeted therapies. The vascular endothelial growth factor (VEGF) pathway has been identified as an important mediator for the development of RCC. Numerous agents target VEGF-mediated signaling, yet resistance and progressive disease still persists. Novel small molecule VEGF inhibitors with high affinity for the VEGF receptor (VEGFR) have been discovered and are currently under investigation for the management of RCC.
The VEGFR pathway, its aberrant signaling, and the agents under development that inhibit VEGFR signaling are discussed. The mechanism(s), pharmacokinetics, pharmacodynamics, efficacy, and toxicity of these investigational agents are also reviewed.
Management of metastatic RCC involves combination immunotherapy or administration of oral VEGFR inhibitors and largely depends on risk stratification. Emerging and investigational oral VEGFR inhibitors, given as monotherapy or in combination with immunotherapy, could augment current treatment approaches and may mitigate toxicities associated with VEGFR inhibition.
近年来，肾细胞癌（RCC）的发病率有所增加，不幸的是，许多患者最初表现为转移性疾病。当手术不是一种选择时，治疗涉及靶向治疗药物的应用。血管内皮生长因子（VEGF）途径已被确定为 RCC 发展的重要介质。许多针对 VEGF 介导的信号的药物已经被发现，但耐药性和进行性疾病仍然存在。新型高亲和力的小分子 VEGF 受体（VEGFR）抑制剂已被发现，并正在研究用于 RCC 的治疗。
讨论了 VEGFR 途径、其异常信号以及正在开发的抑制 VEGFR 信号的药物。还回顾了这些研究药物的机制、药代动力学、药效学、疗效和毒性。
转移性 RCC 的治疗涉及联合免疫疗法或口服 VEGFR 抑制剂，主要取决于风险分层。新兴的和研究中的口服 VEGFR 抑制剂，作为单一疗法或与免疫疗法联合使用，可能会增强当前的治疗方法，并可能减轻与 VEGFR 抑制相关的毒性。
