PMID- 19678801
OWN - NLM
STAT- MEDLINE
DCOM- 20100225
LR  - 20211203
IS  - 1744-7658 (Electronic)
IS  - 1354-3784 (Linking)
VI  - 18
IP  - 9
DP  - 2009 Sep
TI  - Targeting the PI3K/AKT/mTOR signaling network in acute myelogenous leukemia.
PG  - 1333-49
LID - 10.1517/14728220903136775 [doi]
AB  - BACKGROUND: The PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway 
      plays a central role in cell growth, proliferation and survival not only under 
      physiological conditions but also in a variety of tumor cells. Therefore, the 
      PI3K/Akt/mTOR axis may be a critical target for cancer therapy. OBJECTIVE: This 
      review discusses how PI3K/Akt/mTOR signaling network is constitutively active in 
      acute myelogenous leukemia (AML), where it strongly influences proliferation, 
      survival and drug-resistance of leukemic cells, and how effective targeting of 
      this pathway with pharmacological inhibitors, used alone or in combination with 
      existing drugs, may result in suppression of leukemic cell growth, including 
      leukemic stem cells. METHODS: We searched the literature for articles dealing 
      with activation of this pathway in AML and highlighting the efficacy of small 
      molecules directed against the PI3K/Akt/mTOR signaling cascade. CONCLUSIONS: The 
      limit of acceptable toxicity for standard chemotherapy has been reached in AML. 
      Therefore, new therapeutic strategies are needed. Targeting the PI3K/Akt/mTOR 
      signaling network with small molecule inhibitors, alone or in combinations with 
      other drugs, may result in less toxic and more efficacious treatment of AML 
      patients. Efforts to exploit selective inhibitors of the PI3K/Akt/mTOR pathway 
      that show effectiveness and safety in the clinical setting are currently 
      underway.
FAU - Martelli, Alberto M
AU  - Martelli AM
AD  - Universita di Bologna, Dipartimento di Scienze Anatomiche Umane, 40126 Bologna, 
      Italy. alberto.martelli@unibo.it
FAU - Evangelisti, Camilla
AU  - Evangelisti C
FAU - Chiarini, Francesca
AU  - Chiarini F
FAU - Grimaldi, Cecilia
AU  - Grimaldi C
FAU - Manzoli, Lucia
AU  - Manzoli L
FAU - McCubrey, James A
AU  - McCubrey JA
LA  - eng
GR  - R01098195/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Expert Opin Investig Drugs
JT  - Expert opinion on investigational drugs
JID - 9434197
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Small Molecule Libraries)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/adverse 
      effects/*pharmacology/therapeutic use
MH  - Clinical Trials as Topic
MH  - Drug Evaluation, Preclinical
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism/physiology
MH  - Leukemia, Myeloid, Acute/*drug therapy/enzymology/metabolism
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Serine-Threonine Kinases/*metabolism/physiology
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/physiology
MH  - Signal Transduction/*drug effects
MH  - Small Molecule Libraries/administration & dosage/adverse 
      effects/*pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases
RF  - 177
EDAT- 2009/08/15 09:00
MHDA- 2010/02/26 06:00
CRDT- 2009/08/15 09:00
PHST- 2009/08/15 09:00 [entrez]
PHST- 2009/08/15 09:00 [pubmed]
PHST- 2010/02/26 06:00 [medline]
AID - 10.1517/14728220903136775 [doi]
PST - ppublish
SO  - Expert Opin Investig Drugs. 2009 Sep;18(9):1333-49. doi: 
      10.1517/14728220903136775.