Rini Brian I
Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Glickman Urological and Kidney Institute, 9500 Euclid Avenue/Desk R35, Cleveland, OH 44195, USA.
Cancer. 2009 May 15;115(10 Suppl):2306-12. doi: 10.1002/cncr.24227.
Inactivation of the von Hippel-Lindau tumor suppressor gene in most sporadic renal cell carcinoma (RCC) tumors leads to a fundamental reliance on elements of this pathway, namely, the potent proangiogenic factor, vascular endothelial growth factor (VEGF). Thus, VEGF-targeted therapeutics have undergone extensive clinical testing in RCC. Approaches to bind circulating VEGF protein (eg, bevacizumab) and small molecule inhibitors of the receptor on which the VEGF ligand binds (eg, sunitinib, sorafenib, axitinib, and pazopanib) have been tested. Robust clinical effects have been observed, including high objective response rates, prolonged progression-free survival, and evidence of long overall survival for patients with metastatic RCC patients who are treated with these agents. Future directions include investigation of combination and sequenced therapy, elucidation of mechanisms of response and resistance, and exploration of the effect of these agents in other disease settings.
在大多数散发性肾细胞癌（RCC）肿瘤中，冯·希佩尔-林道肿瘤抑制基因的失活导致对该信号通路成分的根本依赖，即强效促血管生成因子血管内皮生长因子（VEGF）。因此，VEGF靶向疗法已在RCC中进行了广泛的临床试验。已测试了结合循环VEGF蛋白的方法（如贝伐单抗）以及VEGF配体所结合受体的小分子抑制剂（如舒尼替尼、索拉非尼、阿昔替尼和帕唑帕尼）。已观察到显著的临床效果，包括高客观缓解率、延长无进展生存期，以及接受这些药物治疗的转移性RCC患者有长期总生存的证据。未来的方向包括联合和序贯治疗的研究、应答和耐药机制的阐明，以及探索这些药物在其他疾病背景下的作用。
