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肾细胞癌治疗的靶向疗法:最新进展与未来展望

Targeted therapies for treatment of renal cell carcinoma: recent advances and future perspectives.

作者信息

Minguet Joan, Smith Katherine H, Bramlage Carsten P, Bramlage Peter

机构信息

European Institute of Cancer Research (EICR), Carrer del Passeig, 2, 08221, Terrassa, Spain,

出版信息

Cancer Chemother Pharmacol. 2015 Aug;76(2):219-33. doi: 10.1007/s00280-015-2770-3. Epub 2015 May 12.

Abstract

PURPOSE

A wide variety of targeted therapies are available for the treatment of renal cancer that has progressed beyond the point at which surgery is a viable option. In addition, there are many more that are in the different stages of clinical trials. Here, we provide a methodical discussion of the efficacy and safety of targeted therapies for the treatment of advanced renal cell carcinoma.

METHODS

We conducted a systematic literature employing the search terms: renal cell carcinoma targets, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and each of the drugs discussed within these papers.

RESULTS

The identified targeted therapies work by disrupting specific signalling pathways involved in tumour progression, such as those responsible for angiogenesis and cell proliferation. Tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors are now established classes of drugs used in the treatment of renal cancer, with a total of six having received regulatory approval to date (sorafenib, sunitinib, pazopanib, axitinib, temsirolimus, and everolimus). Ongoing trials are likely to result in addition to these in the near future, for example, tivozanib, dovitinib, and cediranib. Furthermore, in addition to these small molecule drugs, immunotherapies involving monoclonal antibodies against signalling molecules such as vascular endothelial growth factor (bevacizumab) or programmed death-1 (nivolumab) are receiving increasing attention.

CONCLUSIONS

Targeted therapies have great potential for disrupting tumour progression by inhibiting certain signalling pathways. As our understanding of the biochemical pathways involved in cancer progresses, additional targets are certain to become apparent, expanding treatment options even further.

摘要

目的

对于已发展到手术不再是可行选择阶段的肾癌,有多种靶向治疗方法可供使用。此外,还有更多药物正处于临床试验的不同阶段。在此,我们对晚期肾细胞癌靶向治疗的疗效和安全性进行系统讨论。

方法

我们进行了一项系统文献研究,使用的检索词为:肾细胞癌靶点、酪氨酸激酶抑制剂、雷帕霉素哺乳动物靶点抑制剂以及这些论文中讨论的每种药物。

结果

已确定的靶向治疗通过破坏参与肿瘤进展的特定信号通路发挥作用,例如那些负责血管生成和细胞增殖的信号通路。酪氨酸激酶抑制剂和雷帕霉素哺乳动物靶点抑制剂现已成为用于治疗肾癌的既定药物类别,迄今为止共有六种药物获得了监管批准(索拉非尼、舒尼替尼、帕唑帕尼、阿昔替尼、替西罗莫司和依维莫司)。在不久的将来,正在进行的试验可能会带来更多药物,例如,替沃扎尼、多韦替尼和西地尼布。此外,除了这些小分子药物外,涉及针对信号分子如血管内皮生长因子(贝伐单抗)或程序性死亡-1(纳武单抗)的单克隆抗体的免疫疗法也越来越受到关注。

结论

靶向治疗通过抑制某些信号通路具有极大的破坏肿瘤进展的潜力。随着我们对癌症相关生化途径的理解不断深入,肯定会出现更多靶点,进一步扩大治疗选择。

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