Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Curr Opin Oncol. 2012 May;24(3):284-90. doi: 10.1097/CCO.0b013e328351c646.
This article reviews recent developments in the use of systemic targeted therapies for the treatment of advanced clear and nonclear cell renal cell carcinoma (RCC). The genetic/molecular basis of each form of RCC is discussed and current treatments and clinical trials are described.
The treatment of advanced RCC continues to be a major challenge for uro-oncologists. The rapid growth in therapeutic options has brought much needed improvements in overall and progression-free survival, although durable complete responses remain elusive. The recent identification of mutations in genes involved in chromatin remodeling will likely lead to the investigation of whether components of this critical process can also be valid therapeutic targets in clear cell RCC. Similarly, efforts to decipher the molecular mechanisms underlying nonclear cell variants of RCC are beginning to engender novel therapeutic strategies directed against these rarer forms of kidney cancer. Despite the availability of multiple treatment options, several challenges remain: selecting the best first-line or subsequent therapy for a given patient, the optimal sequencing of the various agents available, designing trials with appropriate comparison arms and endpoints, and identifying well tolerated and effective drug combinations.
Agents targeting the vascular endothelial growth factor and mammalian target of rapamycin pathways remain the mainstay in the management of metastatic RCC. Ongoing and future studies are expected to facilitate the development of therapeutic regimens that incorporate agents with improved tolerability and enhanced efficacy by continuing to capitalize on the strides made by basic and translational scientists in uncovering the mechanisms underlying the various forms of RCC.
本文综述了系统靶向治疗在治疗晚期透明细胞和非透明细胞肾细胞癌（RCC）中的最新进展。讨论了每种 RCC 形式的遗传/分子基础，并描述了当前的治疗方法和临床试验。
晚期 RCC 的治疗仍然是泌尿科肿瘤学家面临的主要挑战。治疗选择的快速增长为总生存期和无进展生存期带来了急需的改善，尽管持久的完全缓解仍然难以实现。最近鉴定的参与染色质重塑的基因中的突变可能会导致研究是否可以将这一关键过程的成分也作为透明细胞 RCC 的有效治疗靶点。同样，为了解非透明细胞 RCC 变体的分子机制而进行的努力也开始产生针对这些更罕见的肾癌形式的新治疗策略。尽管有多种治疗选择，但仍存在一些挑战：为特定患者选择最佳一线或后续治疗，最佳排列各种现有药物，设计具有适当比较臂和终点的试验，以及确定耐受良好且有效的药物组合。
针对血管内皮生长因子和哺乳动物雷帕霉素靶蛋白途径的药物仍然是转移性 RCC 治疗的主要方法。正在进行和未来的研究有望通过继续利用基础和转化科学家在揭示各种 RCC 形式的机制方面取得的进展，促进开发出包含耐受性更好、疗效更高的药物的治疗方案。
