转移性肾细胞癌靶向治疗的分子生物学基础  

Molecular biological foundation of targeted therapy for metastatic renal cell carcinoma

作　　者：来翀[1] 滕晓东[2] 

机构地区：[1]浙江大学医学院附属第一医院泌尿外科,浙江杭州310003 [2]浙江大学医学院附属第一医院病理科,浙江杭州310003

出　　处：《浙江大学学报（医学版）》2016年第1期91-97,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省公益技术应用研究计划

摘　　要：肾细胞癌发病率呈上升趋势，仅部分早期肾细胞癌患者可通过手术而治愈。如何在外科术后对患者进行更精准的抗肿瘤治疗是未来肾细胞癌治疗探索的方向。肾细胞癌中大部分转移性肾细胞癌为肾透明细胞癌，因此针对肾透明细胞癌最具有开发靶向药物的价值。目前靶点基因分子改变明确且具有临床应用价值的仍只有肾透明细胞癌特异性的VHL相关通路的关键蛋白。 VHL的失活引起诸多基因的改变。临床现有的进展期肾透明细胞癌的靶向治疗大多数针对信号通路靶点，其他如程序性死亡蛋白1、抗体药物偶联物药物和干细胞则是针对新抗癌机制。尚无确切的能使大多数肾细胞癌患者受益且在临床广泛应用的治疗方案。本文结合临床经验和文献，对肾透明细胞癌的分子特征、VHL突变通路以及进展期肾透明细胞癌的靶向药物治疗现状和展望进行重点阐述，旨在寻找精确的肾细胞癌治疗靶点，指导临床肾细胞癌的精准化治疗。The incidence of renal cell carcinoma （ RCC） is increasing.Radical cure by surgery can only be achieved in patients with early stage tumors.How to precisely＆amp;nbsp;use antineoplastic agents after surgery is an important problem to be solved.Most metastatic RCCs are pathologically identified as clear cell RCC （ ccRCC ） , thus to develop agents targeting ccRCC is critical.Most clinically available targeted therapies are based on targeting some spots in specific pathways;or based on targeting new anti-tumor mechanisms, such as programmed death-1 （ PD-1 ） , antibody-drug conjugates （ ADC） and stem cells.There is still no targeted therapy having definite effect to most RCC patients.Only von Hippel-Lindau （ VHL） pathway so far has been confirmed to be related to ccRCC development and progression;the inactivation of VHL gene causes many significant downstream gene changes.The key proteins involved in VHL pathway may be potential therapeutic targets for ccRCC.In this article, we review the current progress of targeted therapy for RCC, focus on the molecular characteristics of ccRCC, its relation to VHL pathway, the potential therapeutic targets and future clinical application for metastatic ccRCC.

关 键 词：肾细胞癌 转移性肾细胞癌 肾透明细胞癌 肾癌/精准治疗 肾癌/靶向治疗 综述 

分 类 号：R737.11[医药卫生—肿瘤]