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mTOR 抑制剂治疗晚期肾细胞癌。

mTOR inhibitors in advanced renal cell carcinoma.

机构信息

Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA.

出版信息

Hematol Oncol Clin North Am. 2011 Aug;25(4):835-52. doi: 10.1016/j.hoc.2011.04.008.

DOI:10.1016/j.hoc.2011.04.008
PMID:21763970
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3587783/
Abstract

Better understanding of the molecular biology of renal cell carcinoma (RCC) has led to the development of several targeted anti-cancer agents, several of which have since received approval for treatment of advanced disease. Two of these, the intravenous agent temsirolimus and the oral everolimus, exhibit antitumor effects through inhibition of the mammalian target of rapamycin (mTOR) pathway. This article reviews their mechanisms of action in the context of the current understanding of RCC pathophysiology, the clinical data leading to their approval, class-specific toxicities, potential molecular mechanisms behind treatment resistance and novel treatment approaches for RCC that incorporate mTOR blockade.

摘要

更好地理解肾细胞癌(RCC)的分子生物学导致了几种靶向抗癌药物的发展,其中几种药物已被批准用于治疗晚期疾病。其中两种,静脉注射的替西罗莫司和口服的依维莫司,通过抑制哺乳动物雷帕霉素靶蛋白(mTOR)途径发挥抗肿瘤作用。本文综述了它们在目前对 RCC 病理生理学的理解、导致其批准的临床数据、特定于类别的毒性、治疗耐药背后的潜在分子机制以及包含 mTOR 阻断的 RCC 新治疗方法的背景下的作用机制。

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mTOR inhibitors in advanced renal cell carcinoma.mTOR 抑制剂治疗晚期肾细胞癌。
Hematol Oncol Clin North Am. 2011 Aug;25(4):835-52. doi: 10.1016/j.hoc.2011.04.008.
2
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本文引用的文献

1
Everolimus- and temsirolimus-associated enteritis: report of three cases.
J Clin Oncol. 2011 May 10;29(14):e404-6. doi: 10.1200/JCO.2010.33.5984. Epub 2011 Feb 28.
2
The mammalian target of rapamycin pathway is widely activated without PTEN deletion in renal cell carcinoma metastases.哺乳动物雷帕霉素靶蛋白通路在肾细胞癌转移中广泛激活,而并非由于 PTEN 缺失。
Cancer. 2011 Jan 15;117(2):290-300. doi: 10.1002/cncr.25402. Epub 2010 Sep 9.
3
Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus.人类癌细胞中 PI3K 和 KRAS 信号通路的失调决定了它们对依维莫司的反应。
J Clin Invest. 2010 Aug;120(8):2858-66. doi: 10.1172/JCI37539. Epub 2010 Jul 26.
4
Temsirolimus in VEGF-refractory metastatic renal cell carcinoma.特西罗莫司治疗血管内皮生长因子耐药的转移性肾细胞癌。
Ann Oncol. 2011 Jan;22(1):145-148. doi: 10.1093/annonc/mdq320. Epub 2010 Jul 1.
5
New inhibitors of the mammalian target of rapamycin signaling pathway for cancer.哺乳动物雷帕霉素靶蛋白信号通路抑制剂在癌症治疗中的应用
Expert Opin Investig Drugs. 2010 Aug;19(8):919-30. doi: 10.1517/13543784.2010.499121.
6
Targeting mTOR in cancer: renal cell is just a beginning.靶向 mTOR 治疗癌症:肾细胞肿瘤只是一个开始。
Target Oncol. 2010 Dec;5(4):269-80. doi: 10.1007/s11523-010-0141-x. Epub 2010 Jun 20.
7
Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors.依维莫司治疗转移性肾细胞癌的 3 期临床试验:最终结果和预后因素分析。
Cancer. 2010 Sep 15;116(18):4256-65. doi: 10.1002/cncr.25219.
8
Emergent toxicities associated with the use of mTOR inhibitors in patients with advanced renal carcinoma.晚期肾细胞癌患者使用 mTOR 抑制剂相关的紧急毒性。
Anticancer Drugs. 2010 Jun;21(5):478-86. doi: 10.1097/cad.0b013e32833760bf.
9
Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma.贝伐珠单抗联合依维莫司治疗晚期肾细胞癌的 II 期临床试验。
J Clin Oncol. 2010 May 1;28(13):2131-6. doi: 10.1200/JCO.2009.26.3152. Epub 2010 Apr 5.
10
Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma.晚期肾细胞癌依维莫司治疗后的非传染性肺炎。
Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403. doi: 10.1164/rccm.200911-1720OC. Epub 2010 Mar 1.