State of the science: an update on renal cell carcinoma.
State of the science: an update on renal cell carcinoma.
复制标题
DOI：
10.1158/1541-7786.mcr-12-0117
复制
发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Rathmell WK
中科院分区：
文献类型：
--
作者：
Jonasch E;Futreal PA;Davis IJ;Bailey ST;Kim WY;Brugarolas J;Giaccia AJ;Kurban G;Pause A;Frydman J;Zurita AJ;Rini BI;Sharma P;Atkins MB;Walker CL;Rathmell WK
肾细胞癌（RCC）是一组复杂的疾病，具有重大的社会经济影响，在世界各地的发病率持续上升。随着泌尿肿瘤学领域面临这些趋势，几个重大的基因组和机制发现改变了我们对这多种癌症的核心理解，包括几种新的罕见肾癌亚型。本综述将研究这些新的发现，并将其置于透明细胞RCC（ccRCC）与von Hippel-Lindau（VHL）基因突变和由此产生的异常缺氧诱导因子（HIF）信号传导的良好关联的背景下。探讨了新型ccRCC相关遗传病变对染色质重塑和表观遗传调控的影响。VHL突变对初级纤毛功能，细胞外基质稳态和肿瘤代谢的影响进行了讨论。VHL蛋白质稳定的审查，利用蛋白质稳定机制的目标，重新功能化突变VHL。使用分子工具来理解ccRCC肿瘤的鉴别特征并开发改进的预后和预测算法的转化努力被提出，并总结了ccRCC中最早的分子发现所产生的新疗法。通过对ccRCC的关键基因组和分子生物学疾病特征进行综合审查，并将这些数据置于不断发展的治疗环境中，我们打算促进参与治疗这种毁灭性疾病的基础，转化和临床研究人员之间的互动，并加速其最终根除的进展。
Renal cell carcinomas (RCC) are emerging as a complex set of diseases with major socioeconomic impact and a continued rise in incidence throughout the world. As the field of urologic oncology faces these trends, several major genomic and mechanistic discoveries have altered our core understanding of this multitude of cancers, including several new rare subtypes of renal cancers. This review will examine these new findings, and place them in the context of the well-established association of clear cell RCC (ccRCC) with mutations in the von Hippel-Lindau (VHL) gene and resultant aberrant hypoxia inducible factor (HIF) signaling. The impact of novel ccRCC-associated genetic lesions on chromatin remodeling and epigenetic regulation is explored. The effects of VHL mutation on primary ciliary function, extracellular matrix homeostasis, and tumor metabolism are discussed. VHL proteostasis is reviewed, with the goal of harnessing the proteostatic machinery to refunctionalize mutant VHL. Translational efforts using molecular tools to understand discriminating features of ccRCC tumors and develop improved prognostic and predictive algorithms are presented and new therapeutics arising from the earliest molecular discoveries in ccRCC are summarized. By creating an integrated review of the key genomic and molecular biological disease characteristics of ccRCC and placing these data in the context of the evolving therapeutic landscape, we intend to facilitate interaction between basic, translational and clinical researchers involved in the treatment of this devastating disease, and accelerate progress towards its ultimate eradication.