Please wait a minute...
浙江大学学报(医学版)  2016, Vol. 45 Issue (1): 91-97    DOI: 10.3785/j.issn.1008-9292.2016.01.15
来翀1, 滕晓东2
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
Molecular biological foundation of targeted therapy for metastatic renal cell carcinoma
LAI Chong1, TENG Xiaodong2
1. Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
2. Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
全文: PDF(914 KB)  


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    

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 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.

Key wordsRenal cell carcinoma    Metastatic renal cell carcinoma    Clear cell renal cell carcinoma    Renal carcinoma/precision treatment    Renal carcinoma/targeted therapy    Review
收稿日期: 2015-08-25      出版日期: 2015-12-12
CLC:  R73  


通讯作者: 滕晓东(1964-),男,硕士,主任医师,主要从事临床病理诊断研究;;     E-mail:
作者简介: 来翀(1988-),女,博士,主治医师,主要从事肾癌发生发展及肾癌复发转移相关的分子病理学及临床应用研究;;
E-mail Alert


来翀 等. 转移性肾细胞癌靶向治疗的分子生物学基础[J]. 浙江大学学报(医学版), 2016, 45(1): 91-97.
LAI Chong, TENG Xiaodong. Molecular biological foundation of targeted therapy for metastatic renal cell carcinoma. Journal of ZheJiang University(Medical Science), 2016, 45(1): 91-97.

链接本文:      或

[1] GIRGIS H, MASUI O, WHITE N M, et al. Lactate dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma[J]. Mol Cancer, 2014, 13:101.
[2] SIEGEL R L, FEDEWA S A, MILLER K D, et al. Cancer statistics for Hispanics/Latinos, 2015[J]. CA Cancer J Clin, 2015, 65(6):457-480.
[3] FERLAY J, SHIN H R, BRAY F, et al. Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008[J]. Int J Cancer, 2010, 127(12):2893-2917.
[4] 吴阶平,那彦群,叶章群,等. 2014版中国泌尿外科疾病诊断治疗指南[M].北京:人民卫生出版社,2013:3-10. WU Jieping, NA Yanqun, YE Zhangqun, et al. Chinese association of urology guidelines the 2014 edition[M]. Beijing:People's Medical Publishing House, 2013:3-10.(in Chinese)
[5] MOTZER R J, BANDER N H, NANUS D M. Renal-cell carcinoma[J]. N Eng J Med, 1996, 335(12):865-875.
[6] TENG J, GAO Y, CHEN M, et al. Prognostic value of clinical and pathological factors for surgically treated localized clear cell renal cell carcinoma[J]. Chin Med J (Engl), 2014, 127(9):1640-1644.
[7] YANG F, ZHOU X, DU S, et al. LIM and SH3 domain protein 1(LASP-1) overexpression was associated with aggressive phenotype and poor prognosis in clear cell renal cell cancer[J]. PLoS One, 2014, 9(6):e100557.
[8] BABAIAN K N, MERRILL M M, MATIN S, et al. Partial nephrectomy in the setting of metastatic renal cell carcinoma[J]. J Urol, 2014, 192(1):36-42.
[9] EBLE J N, SAUTER G, EPSTEIN J I, et al. Pathology and genetics of tumors of the urinary system and male genital organs[M]. Lyon:World Health Organization International Agencg of Reserch on Cancer, 2004:10-40.
[10] 赵明, 滕晓东,孙柯,等. 新近认识的肾细胞癌[J]. 中华病理学杂志, 2013,42(7):478-482. ZHAO Ming, TENG Xiaodong, SUN Ke, et al. Recently identified renal cell carcinoma[J]. Chinese Journal of Pathology, 2013, 42(7):478-482. (in Chinese)
[11] CAIRNS P. Renal cell carcinoma[J]. Cancer Biomark, 2010, 9(1-6):461-473.
[12] SU D, SINGER E A, SRINIVAS A N R. Molecular pathways in renal cell carcinoma:recent advances in genetics and molecular biology[J]. Curr Opin Oncol, 2015, 27(3):217-223.
[13] DALGLIESH G L, FURGE K, GREENMAN C, et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes[J]. Nature, 2010, 463(7279):360-363.
[14] DULAIMI E, IBANEZ DE CACERES I, UZZO R G, et al. Promoter hypermethylation profile of kidney cancer[J]. Clin Cancer Res, 2004,10(12 Pt 1):3972-3979.
[15] VARELA I, TARPEY P, RAINE K, et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma[J]. Nature, 2011, 469(7331):539-542.
[16] Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma[J]. Nature, 2013, 499(7456):43-49.
[17] KAPUR P, PEÑA-LIOPIS S, CHRISTIE A, et al. Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma:a retrospective analysis with independent validation[J]. Lancet Oncol, 2013, 14(2):159-167.
[18] EDMUNDS J W, MAHADEVAN L C, CLAYTON A L. Dynamic histone H3 methylation during gene induction:HYPB/Setd2 mediates all H3K36 trimethylation[J]. EMBO J, 2008, 27(2):406-420.
[19] LI F, MAO G, TONG D, et al. The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα[J]. Cell, 2013, 153(3):590-600.
[20] PEÑA-LIOPIS S, VEGA-RUBÍN-DE-CELIS S, LIAO A, et al. BAP1 loss defines a new class of renal cell carcinoma[J]. Nat Genet, 2012, 44(7):751-759.
[21] SATO Y, YOSHIZATO T, SHIRAISHI Y, et al. Integrated molecular analysis of clear-cell renal cell carcinoma[J]. Nat Genet, 2013, 45(8):860-867.
[22] GORDAN J D, LAL P, DONDETI V R, et al. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma[J]. Cancer Cell, 2008, 14(6):435-446.
[23] MONZON J G, HENG D Y. Management of metastatic kidney cancer in the era of personalized medicine[J]. Crit Rev Clin Lab Sci, 2014, 51(2):85-97.
[24] BRAHMER J R, DRAKE C G, WOLLNER I, et al. Phase I study of single-agent anti-programmed death-1(MDX-1106) in refractory solid tumors:safety, clinical activity, pharmacodynamics, and immunologic correlates[J]. J Clin Oncol, 2010, 28(19):3167-3175.
[25] ZHA Y Y, BLANK C, GAJEWSKI T F. Negative regulation of T-cell function by PD-1[J]. Crit Rev Immunol, 2004, 24(4):229-237.
[26] LAW C L, GORDON K A, TOKI B E, et al. Lymphocyte activation antigen CD70 expressed by renal cell carcinoma is a potential therapeutic target for anti-CD70 antibody-drug conjugates[J]. Cancer Res, 2006, 66(4):2328-2337.
[27] BUSSOLATI B, BROSSA A, CAMUSSI G. Resident stem cells and renal carcinoma[J]. Int J Nephrol, 2011, 2011:286985.
[28] BUSSOLATI B, BRUNO S, GRANGE C, et al. Identification of a tumor-initiating stem cell population in human renal carcinomas[J]. FASEB J, 2008, 22(10):3696-3705.
[29] KANESVARAN R, TAN M H. Targeted therapy for renal cell carcinoma:the next lap[J]. J Carcinog, 2014, 13:3.
[1] 高思倩,沈咏梅,耿福能,李艳华,高建青. 颞叶癫痫与海马成体神经再生[J]. 浙江大学学报(医学版), 2017, 46(1): 97-105.
[2] 王颖,汪仪,陈忠. 中枢胆碱能系统与癫痫关系的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 15-21.
[3] 高思倩,沈咏梅,耿福能,李艳华,高建青. 糖尿病溃疡动物模型的建立及相关治疗研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 97-105.
[4] 李文龙,瞿海斌. 近红外光谱应用于中药质量控制及生产过程监控的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 80-88.
[5] 郑艳榕,张翔南,陈忠. Nix介导的线粒体自噬机制的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 92-96.
[6] 封盛 等. 糖皮质激素受体信号通路在膀胱癌治疗中的作用研究进展[J]. 浙江大学学报(医学版), 2016, 45(6): 655-660.
[7] 李统宇 等. 杜氏肌营养不良疾病模型及基因治疗研究进展[J]. 浙江大学学报(医学版), 2016, 45(6): 648-654.
[8] 曹鹏 等. 双氢青蒿素抗肿瘤分子生物学机制研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 501-507.
[9] 李亭亭 等. 中性粒细胞在哮喘中作用的研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 544-549.
[10] 王雪 等. TANK结合激酶1在抗病毒免疫应答中的作用研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 550-557.
[11] 杜苗苗 等. 钙化性主动脉瓣疾病药物治疗研究进展[J]. 浙江大学学报(医学版), 2016, 45(4): 432-438.
[12] 何斌 等. 贝伐珠单克隆抗体在难治性子宫颈癌中的应用进展[J]. 浙江大学学报(医学版), 2016, 45(4): 395-402.
[13] 历雪莹 等. DNA甲基化及其靶向治疗在急性髓系白血病中的研究进展[J]. 浙江大学学报(医学版), 2016, 45(4): 387-394.
[14] 竺天虹 等. 上皮间充质转化介导子宫内膜异位症发生发展的研究进展[J]. 浙江大学学报(医学版), 2016, 45(4): 439-445.
[15] 徐玉兰 等. 秀丽隐杆线虫神经胶质细胞对神经系统发育和功能的影响[J]. 浙江大学学报(医学版), 2016, 45(3): 315-322.