Jones Jon, Libermann Towia A
Beth Israel Deaconess Medical Center and Harvard Medical School, 4 Blackfan Circle, Boston, MS 02115, USA.
Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):685s-692s. doi: 10.1158/1078-0432.CCR-06-1867.
Renal cell cancer (RCC) is the most lethal of the urological cancers and accounts for 3% of all adult malignancies. Despite numerous recent advances in diagnostic imaging, surgical therapy, and basic molecular understanding, many patients still experience metastatic disease. For metastatic disease patients, response rates to conventional therapies rarely exceed 15% to 25% and are associated with serious adverse effects. The recent development of novel targeted therapies based on the precise biological pathways deregulated in a particular patient has paved the way for individualized, targeted patient management. Nevertheless, to achieve this goal, it is important to delineate the molecular mechanisms underlying cancer development and progression. Genomic approaches have revolutionized the field of cancer research and have led to the rapid discovery of multiple, parallel disease hypotheses, which ultimately have to be validated in large cohorts of patients and in downstream biological experiments for translation into clinical applications. The variable course of RCC and, until recently, a paucity of therapeutic options in the event of metastasis have led to the search for diagnostic and prognostic markers. We and others have used transcriptional profiling to classify different subtypes of RCC and to identify subtype- and metastasis-specific gene signatures predictive for outcome. We discuss herein recent genomic approaches to RCC and the emerging biological pathways underlying RCC development and progression. We also speculate how genomics may affect drug development and the management of patients with RCC.
肾细胞癌（RCC）是泌尿系统癌症中致死率最高的，占所有成人恶性肿瘤的3%。尽管近年来在诊断成像、手术治疗以及基础分子认识方面取得了诸多进展，但仍有许多患者发生转移性疾病。对于转移性疾病患者，传统疗法的缓解率很少超过15%至25%，且伴有严重的不良反应。基于特定患者中失调的精确生物学途径而开发的新型靶向疗法，为个体化、靶向性的患者管理铺平了道路。然而，要实现这一目标，明确癌症发生和发展的分子机制至关重要。基因组学方法彻底改变了癌症研究领域，并促使人们迅速发现了多个并行的疾病假说，最终这些假说必须在大量患者队列以及下游生物学实验中得到验证，才能转化为临床应用。RCC病程多变，而且直到最近，发生转移时治疗选择仍很有限，这促使人们寻找诊断和预后标志物。我们以及其他研究人员已利用转录谱分析对RCC的不同亚型进行分类，并识别出可预测预后的亚型特异性和转移特异性基因特征。我们在此讨论RCC的最新基因组学方法以及RCC发生和发展背后新出现的生物学途径。我们还推测基因组学可能如何影响药物开发以及RCC患者的管理。
