[The PI3K/Akt/mTOR pathway: a new therapeutic target in the treatment of acute myeloid leukemia].
Despite important progress in the therapy of acute myeloid leukaemia (AML) most patients relapse and die from the disease, underlying the need for potent and more specific drugs for the treatment of this pathology. Recently, we demonstrated that the PI3-kinase-Akt-mTOR (mammalian target of rapamycin) pathway is constitutively activated in about 60% of AML patients cells. In vitro, low doses of the specific inhibitor of mTOR, rapamycin, block the phosphorylation of the classical targets of this kinase and inhibit the proliferation of leukemic progenitors without affecting the growth of normal haematopoietic progenitors. The results of this preclinical study led us to investigate the activity of rapamycin in relapsed, refractory, or poor-risk AML patients. The results of this study will be discussed in the review.
Dos Santos
Cédric
C
Inserm U563, CPTP, IFR30, Département d'oncogenèse et signalisation dans les cellules hématopoïétiques, 31024 Toulouse.
Récher
Christian
C
Demur
Cécile
C
Payrastre
Bernard
B
D000208:Acute Disease; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human