m-TOR inhibitors and their potential role in haematological malignancies

被引：53

作者：

Calimeri, Teresa ^{[1
]}

Ferreri, Andres J. M. ^{[1
]}

机构：

[1] IRCCS, San Raffaele Sci Inst, Unit Lymphoid Malignancies, Dept Oncohaematol, Via Olgettina 60, I-20132 Milan, Italy

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2017年 / 177卷 / 05期

关键词：

temsirolimus; everolimus; mTOR inhibitor; lymphoma; myeloma; leukaemia; REFRACTORY MULTIPLE-MYELOMA; RELAPSED MANTLE CELL; PHASE-II TRIAL; PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA; SINGLE-AGENT TEMSIROLIMUS; ADVANCED SOLID TUMORS; NON-HODGKIN-LYMPHOMA; MAMMALIAN TARGET; MTOR INHIBITOR;

D O I：

10.1111/bjh.14529

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 Waldenstrom 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.

引用

页码：684 / 702

页数：19

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