m-TOR inhibitors and their potential role in haematological malignancies.
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.
Unit of Lymphoid Malignancies, Department of Onco-Haematology, IRCCS San Raffaele Scientific Institute, Milano, Italy.
Teresa
T
Calimeri
Unit of Lymphoid Malignancies, Department of Onco-Haematology, IRCCS San Raffaele Scientific Institute, Milano, Italy.
Andrés J M
AJM
Ferreri
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000068338:Everolimus / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
D000903:Antibiotics, Antineoplastic; D000081082:Phosphoinositide-3 Kinase Inhibitors; C515074:ridaforolimus; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
everolimus; leukaemia; lymphoma; mTOR inhibitor; myeloma; temsirolimus