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mTOR抑制剂在肾细胞癌治疗中的未来前景。

Future perspectives for mTOR inhibitors in renal cell cancer treatment.

作者信息

Czarnecka Anna M, Kornakiewicz Anna, Lian Fei, Szczylik Cezary

机构信息

Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, Szaserow 128, 04-141, Warsaw, Poland.

出版信息

Future Oncol. 2015;11(5):801-17. doi: 10.2217/fon.14.303.

Abstract

Everolimus is a mTOR inhibitor that demonstrates antitumor and antiangiogenic activities. In a randomized Phase III trial, patients with metastatic renal cell carcinoma who progressed on sunitinib/sorafenib were treated with everolimus and showed significant improvement in progression-free survival compared with best supportive care. Novel approaches in treatment are expected to ensure less toxic therapies and increase efficacy of everolimus. To provide a new perspective for mTOR inhibitor research and therapy, we discuss renal cell carcinoma cancer stem cells as a potential target for mTOR inhibitors and present new concepts on emerging antiangiogenic therapies. Finally, we point why systems biology approach with reverse molecular engineering may also contribute to the field of drug discovery in renal cell carcinoma.

摘要

依维莫司是一种具有抗肿瘤和抗血管生成活性的mTOR抑制剂。在一项随机III期试验中,对舒尼替尼/索拉非尼治疗后病情进展的转移性肾细胞癌患者使用依维莫司治疗,与最佳支持治疗相比,无进展生存期有显著改善。预计新的治疗方法可确保毒性更小的治疗并提高依维莫司的疗效。为了为mTOR抑制剂的研究和治疗提供新视角,我们讨论了肾细胞癌癌症干细胞作为mTOR抑制剂的潜在靶点,并介绍了新兴抗血管生成疗法的新概念。最后,我们指出为什么采用反向分子工程的系统生物学方法也可能有助于肾细胞癌药物发现领域。

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