PMID- 24904824
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140624
LR  - 20211021
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 4
DP  - 2014
TI  - Targeting the PI3K/mTOR Pathway in Pediatric Hematologic Malignancies.
PG  - 108
LID - 10.3389/fonc.2014.00108 [doi]
LID - 108
AB  - A complex interplay of intracellular signaling networks orchestrates normal cell 
      growth and survival, including translation, transcription, proliferation, and 
      cell cycle progression. Dysregulation of such signals occurs commonly in many 
      malignancies, thereby giving the cancer cell a survival advantage, but also 
      providing possible targets for therapeutic intervention. Activation of the 
      phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of 
      rapamycin (mTOR) signaling pathway contributes to the proliferative advantage of 
      malignant cells and may confer resistance to chemotherapy in various hematologic 
      malignancies. The initial mTOR inhibitor, sirolimus (also known as rapamycin), 
      was first discovered in 1975 in the soil of Easter Island. Sirolimus was 
      originally developed as an anti-fungal agent given its macrolide properties, but 
      was approved by the Food and Drug Administration (FDA) in 1999 as an 
      immunosuppressive agent for renal transplantation patients once its T cell 
      suppression characteristics were recognized. Shortly thereafter, recognition of 
      sirolimus's ability to inhibit cellular proliferation and cell cycle progression 
      brought sirolimus to the forefront as a possible inhibitor of mTOR. In the 
      subsequent decade, the functional roles of the mTOR protein have been more fully 
      elucidated, and this protein is now known to be a key regulator in a highly 
      complex signaling pathway that controls cell growth, proliferation, metabolism, 
      and apoptosis. This article discusses the dysregulation of PI3K/mTOR signaling in 
      hematologic malignancies, including acute and chronic leukemias, lymphomas, and 
      lymphoproliferative disorders. The current repertoire of PI3K/mTOR pathway 
      inhibitors in development and clinical trials to date are described with emphasis 
      upon pediatric hematologic malignancies (Figure 1). Investigation of small 
      molecule inhibitors of this complex signaling network is an active area of 
      oncology drug development.
FAU - Tasian, Sarah K
AU  - Tasian SK
AD  - Division of Oncology, Department of Pediatrics, The Children's Hospital of 
      Philadelphia, University of Pennsylvania School of Medicine , Philadelphia, PA , 
      USA.
FAU - Teachey, David T
AU  - Teachey DT
AD  - Division of Oncology, Department of Pediatrics, The Children's Hospital of 
      Philadelphia, University of Pennsylvania School of Medicine , Philadelphia, PA , 
      USA.
FAU - Rheingold, Susan R
AU  - Rheingold SR
AD  - Division of Oncology, Department of Pediatrics, The Children's Hospital of 
      Philadelphia, University of Pennsylvania School of Medicine , Philadelphia, PA , 
      USA.
LA  - eng
GR  - T32 CA128583/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20140516
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC4032892
OTO - NOTNLM
OT  - Hodgkin lymphoma
OT  - PI3K/mTOR
OT  - acute lymphoblastic leukemia
OT  - acute myeloid leukemia
OT  - clinical trial
OT  - non-Hodgkin lymphoma
OT  - pediatric
OT  - tyrosine kinase inhibitors
EDAT- 2014/06/07 06:00
MHDA- 2014/06/07 06:01
PMCR- 2014/01/01
CRDT- 2014/06/07 06:00
PHST- 2014/02/27 00:00 [received]
PHST- 2014/04/30 00:00 [accepted]
PHST- 2014/06/07 06:00 [entrez]
PHST- 2014/06/07 06:00 [pubmed]
PHST- 2014/06/07 06:01 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2014.00108 [doi]
PST - epublish
SO  - Front Oncol. 2014 May 16;4:108. doi: 10.3389/fonc.2014.00108. eCollection 2014.