Beatson West of Scotland Cancer Centre, Glasgow, UK.
Anticancer Agents Med Chem. 2010 Mar;10(3):225-35. doi: 10.2174/1871520611009030225.
A better understanding of the molecular biology of renal cell carcinoma (RCC) and the emergence of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment for patients with metastatic RCC (mRCC). Multikinase inhibitors (sunitinib and sorafenib) and the inhibitors of mammalian target of rapamycin (temsirolimus and everolimus) have recently shown superiority over IFN-alpha or placebo; and bevacizumab + IFN-alpha have demonstrated improved activity when compared to IFN-alpha alone in patients with mRCC. Newer anti-vascular endothelial growth factor (VEGF) agents such as axitinib, pazopanib and cediranib are currently under investigation to expand and elucidate future treatment options. Several studies have investigated the synergistic potential of TKIs with a view to blocking multiple signalling pathways simultaneously, but this approach has resulted in a significant increase in toxicity. Sequential TKI administration has demonstrated encouraging results but the optimal sequence of TKIs is yet to be determined. Studies combining TKIs with immunotherapy have resulted in varying degrees of success; with bevacizumab + IFN-alpha being the only studies with positive outcomes. The purpose of this review is to summarize the current evidence supporting the role of TKIs and to discuss potential future directions in the management of mRCC. The role of TKIs as monotherapy, in combination with immunotherapy or other TKIs (combined or sequential approach) will be discussed.
更好地理解肾细胞癌（RCC）的分子生物学和酪氨酸激酶抑制剂（TKIs）的出现彻底改变了转移性肾细胞癌（mRCC）患者的治疗方法。多激酶抑制剂（舒尼替尼和索拉非尼）和哺乳动物雷帕霉素靶蛋白抑制剂（替西罗莫司和依维莫司）最近已被证明优于 IFN-α或安慰剂；贝伐单抗+IFN-α与单独使用 IFN-α相比，在 mRCC 患者中显示出更好的疗效。新型抗血管内皮生长因子（VEGF）药物如阿昔替尼、帕唑帕尼和西地尼布目前正在研究中，以扩大和阐明未来的治疗选择。一些研究已经调查了 TKI 与免疫疗法联合使用的协同潜力，以期同时阻断多个信号通路，但这种方法导致毒性显著增加。序贯 TKI 给药已显示出令人鼓舞的结果，但 TKI 的最佳顺序尚未确定。联合 TKI 与免疫疗法的研究取得了不同程度的成功；贝伐单抗+IFN-α是唯一具有阳性结果的研究。本综述的目的是总结支持 TKI 作用的现有证据，并讨论 mRCC 管理的潜在未来方向。将讨论 TKI 作为单一疗法、与免疫疗法联合或与其他 TKI（联合或序贯方法）联合的作用。
