Kruck Stephan, Merseburger Axel S, Stenzl Arnulf, Bedke Jens
Department of Urology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler Strasse 3, 72076, Tuebingen, Germany,
World J Urol. 2014 Feb;32(1):69-77. doi: 10.1007/s00345-013-1096-1. Epub 2013 May 9.
The proliferative control of renal cell cancer (RCC) via vascular endothelial growth factor and mammalian target of rapamycin inhibition by targeted agents has substantially improved survival rates for RCC patients with metastatic (m) disease. However, the management of mRCC remains challenging because some patients are primarily refractory to the approved targeted agents and most therapies eventually fail because of the development of an intractable drug resistance. Tumor progression is closely related to a persistent or restored proliferation via direct and indirect oncogenic signals. Although the elucidation of cancer cell proliferation in the "-omics era" has revealed an enormous number of new potential targets, a comprehensive overview of the different pathways that might serve as new drug targets has become increasingly complex.
METHODS/RESULTS: This review highlights the well-trodden pathways in mRCC that are inhibited by targeting agents and describes innovative modes of action within these pathways that are currently not targeted but are under exploration in clinical studies. Additionally, this paper highlights as future drug targets the components of tumor metabolism that supply the tumor cells with nutrition.
These fundamental insights into RCC proliferation as a key driver of progression are urgently needed to overcome the currently improved but still limited targeted drug success.
通过靶向药物抑制血管内皮生长因子和雷帕霉素哺乳动物靶点来对肾细胞癌（RCC）进行增殖控制，已显著提高了转移性（m）疾病RCC患者的生存率。然而，mRCC的管理仍然具有挑战性，因为一些患者对已获批的靶向药物原发性难治，并且大多数治疗最终因顽固性耐药的出现而失败。肿瘤进展通过直接和间接致癌信号与持续或恢复的增殖密切相关。尽管在“组学时代”对癌细胞增殖的阐明揭示了大量新的潜在靶点，但对可能作为新药物靶点的不同途径进行全面概述已变得日益复杂。
方法/结果：本综述重点介绍了mRCC中被靶向药物抑制的常见途径，并描述了这些途径中目前未被靶向但正在临床研究中探索的创新作用模式。此外，本文强调将为肿瘤细胞提供营养的肿瘤代谢成分作为未来的药物靶点。
迫切需要对RCC增殖作为进展的关键驱动因素有这些基本认识，以克服目前虽有所改善但仍然有限的靶向药物治疗效果。
