title: [m-TOR inhibitors: biology and use in the treatment of haematological diseases].
abstract: Mammalian target of rapamycyin (mTOR) is a downstream serine/threonine kinase of the PI3K/AKT pathway that integrates signals from the microenvironment such as cytokines, growth factors, and nutriments to regulate multiple cellular processes, including mRNA translation, autophagy, metabolism, growth and survival. mTOR operates in two distinct multi-protein complexes: mTORC1 and mTORC2; sharing mTOR kinase as a common catalytic subunit, mTORC1 controls cell growth and mTORC2 modulates cell survival and drug resistance. mTOR signalling pathway has been found to be deregulated in many haematological malignancies, and has been designed as an attractive anti-tumor target. Thereby, mTOR inhibition with rapamycin (sirolimus) or its derivates (rapalogs) represents promising treatments, either alone or in combination with strategies to target other pathways that may overcome resistance. At present time, numerous clinical trials with mTOR inhibitors are ongoing for treatment of haematological diseases with modest or promising results. The aim of this review is to present the rationale for using mTOR inhibitors in haematology, first via biological explanations and secondly, by focusing on each haematological malignancies with new perspective of treatment.
authors.affiliation: Institut de cancérologie de la Loire, service d'hématologie clinique, Saint-Priest-en-Jarez, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Balsat
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cornillon
mesh_terms: D004789:Enzyme Activation; D006402:Hematologic Diseases / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D000076222:Mechanistic Target of Rapamycin Complex 1; D009101:Multiple Myeloma / Q000188:drug therapy; D046912:Multiprotein Complexes; D011506:Proteins / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
chemical_list: C493245:CRTC2 protein, human; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases