Department of Renal Medicine, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
Int J Biochem Cell Biol. 2011 Nov;43(11):1537-49. doi: 10.1016/j.biocel.2011.08.003. Epub 2011 Aug 12.
Renal cell carcinoma (RCC), the commonest type of kidney cancer, is a highly metastatic and the deadliest of all urologic cancers. Despite the development of many novel chemotherapeutics in recent years, metastatic RCC remains an incurable and lethal disease. The imperative for the identification of novel molecular targets and more effective therapeutics for metastatic RCC remain. One promising target is the transcription factor nuclear factor kappa B (NF-κB). NF-κB is unique in the sense that it regulates all important aspects of RCC biology that pose challenge to conventional therapy - resistance to apoptosis, angiogenesis and multi-drug resistance. Aberrations in the von Hippel Lindau gene (VHL) are the most important risk factor for the development of RCC, especially the clear cell type, which constitutes 70-80% of RCC. VHL is a negative regulator of NF-κB. In the absence of a functional VHL, the expression and activity of NF-κB are enhanced, which subsequently confer drug resistance and promote epithelial-mesenchymal-transition of RCC. This review provides an overview of RCC, its molecular mechanisms, the role of NF-κB in carcinomas including RCC, and the rationale for NF-κB as a target molecule.
肾细胞癌（RCC）是最常见的肾癌类型，是所有泌尿科癌症中转移率最高、最致命的一种。尽管近年来开发了许多新型化疗药物，但转移性 RCC 仍然是一种无法治愈的致命疾病。因此，仍然需要确定新型分子靶点和更有效的转移性 RCC 治疗方法。转录因子核因子 kappa B（NF-κB）是一个很有前途的靶点。NF-κB 的独特之处在于，它调节了肾癌生物学的所有重要方面，这些方面对传统疗法构成了挑战——抗细胞凋亡、血管生成和多药耐药性。von Hippel Lindau 基因（VHL）的异常是 RCC 发展的最重要危险因素，特别是透明细胞型，占 RCC 的 70-80%。VHL 是 NF-κB 的负调节因子。在缺乏功能性 VHL 的情况下，NF-κB 的表达和活性增强，从而导致耐药性，并促进 RCC 的上皮-间充质转化。这篇综述概述了 RCC 的分子机制、NF-κB 在包括 RCC 在内的癌症中的作用，以及将 NF-κB 作为靶点分子的合理性。
