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m‐ TOR inhibitors and their potential role in haematological malignancies
Author(s) -
Calimeri Teresa,
Ferreri Andrés J. M.
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14529
Subject(s) - pi3k/akt/mtor pathway , lymphoma , multiple myeloma , cancer research , medicine , cancer , immunology , biology , signal transduction , biochemistry
Summary It is widely demonstrated that the PI 3K‐ 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 PI 3K‐ 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.