Calimeri Teresa, Ferreri Andrés J M
Unit of Lymphoid Malignancies, Department of Onco-Haematology, IRCCS San Raffaele Scientific Institute, Milano, Italy.
Br J Haematol. 2017 Jun;177(5):684-702. doi: 10.1111/bjh.14529. Epub 2017 Feb 1.
It is widely demonstrated that the PI3K-AKT-mTOR signalling is critical in normal myeloid and lymphoid development and function. Thus, it is not strange that this pathway is often deregulated in haematological tumours, providing a strong preclinical rationale for the use of drugs targeting the PI3K-AKT-mTOR axis in haematological malignancies. The main focus of this review is to examine the mammalian target of rapamycin (mTOR, also termed mechanistic target of rapamycin [MTOR]) signalling pathways and to provide a brief overview of rapalogs and second-generation mTOR inhibitors used to target its aberrant activation in cancer treatment. We will also discuss the results obtained with the use of these agents in patients with acute leukaemia, Hodgkin lymphoma, non-Hodgkin lymphomas, multiple myeloma and Waldenström macroglobulinaemia. Ongoing clinical trials in haematological malignancies that are investigating first- and second-generation mTOR inhibitors as single agents and as components of combination regimens are also presented.
广泛的研究表明，PI3K-AKT-mTOR信号通路在正常髓系和淋巴系发育及功能中起关键作用。因此，该通路在血液肿瘤中常常失调并不奇怪，这为在血液系统恶性肿瘤中使用靶向PI3K-AKT-mTOR轴的药物提供了强有力的临床前理论依据。本综述的主要重点是研究雷帕霉素哺乳动物靶点（mTOR，也称为雷帕霉素机制靶点[MTOR]）信号通路，并简要概述用于在癌症治疗中靶向其异常激活的雷帕霉素类似物和第二代mTOR抑制剂。我们还将讨论这些药物在急性白血病、霍奇金淋巴瘤、非霍奇金淋巴瘤、多发性骨髓瘤和华氏巨球蛋白血症患者中使用的结果。还介绍了正在进行的血液系统恶性肿瘤临床试验，这些试验正在研究第一代和第二代mTOR抑制剂作为单一药物以及作为联合治疗方案的组成部分的情况。
