Evaluating temsirolimus activity in multiple tumors: a review of clinical trials.
Evaluating temsirolimus activity in multiple tumors: a review of clinical trials.
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DOI：
10.1053/j.seminoncol.2009.10.010
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发表时间：
2009-12-01
影响因子：
4
通讯作者：
Purvis, Joseph
中科院分区：
文献类型：
--
作者：
Dancey, Janet E;Curiel, Rafael;Purvis, Joseph
哺乳动物雷帕霉素靶点（mTOR）信号的激活发生在多种人类肿瘤中，并可导致对mTOR抑制剂的易感性增加。Temsirolimus是一种新型的雷帕霉素类似物，无论是单独使用还是与化疗或其他靶向药物联合使用，都显示出在各种实体和血液肿瘤类型的临床前和临床早期抗肿瘤活性。随机III期试验已经证明单药替西莫司治疗晚期肾细胞癌和复发和/或难治性套细胞淋巴瘤的临床疗效显著。在I期和II期试验中研究的其他恶性肿瘤包括胶质母细胞瘤、乳腺癌、子宫内膜癌、非霍奇金淋巴瘤和多发性骨髓瘤。本文综述了迄今为止报道的替西莫司治疗各种实体和血液恶性肿瘤的临床试验结果，以及正在进行的试验中测试的当前策略。替西莫司在多种肿瘤中的研究结果为未来开发替西莫司和其他mTOR抑制剂提供了有价值的框架。
Activation of mammalian target of rapamycin (mTOR) signaling occurs in a wide variety of human tumors and can lead to increased susceptibility to mTOR inhibitors. Temsirolimus, a novel analog of rapamycin, has shown promising preclinical and early clinical anti-tumor activity in various solid and hematologic tumor types, either alone or in combination with chemotherapy or other targeted agents. Randomized phase III trials have already demonstrated significant clinical benefits of treatment with single-agent temsirolimus in advanced renal cell carcinoma and relapsed and/or refractory mantle cell lymphoma. Other malignancies studied in the phase I and II trial settings include glioblastoma, breast cancer, endometrial cancer, non-Hodgkin lymphomas, and multiple myeloma. This article reviews a comprehensive collection of the clinical trial results reported to date for temsirolimus in various solid and hematologic malignancies, as well as current strategies being tested in ongoing trials. The findings with temsirolimus in multiple tumors provide a valuable framework for future development of temsirolimus and other mTOR inhibitors.