PMID- 18345718
OWN - NLM
STAT- MEDLINE
DCOM- 20080808
LR  - 20211020
IS  - 1174-5878 (Print)
IS  - 1174-5878 (Linking)
VI  - 10
IP  - 2
DP  - 2008
TI  - Molecularly targeted therapies for pediatric acute myeloid leukemia: progress to 
      date.
PG  - 85-92
AB  - While acute myeloid leukemia (AML) is significantly less common than acute 
      lymphoblastic leukemia (ALL) in childhood, it is significantly more deadly with 
      only half as many children likely to be cured with standard therapy. In addition, 
      the typical treatment for AML is among the most toxic of treatments for pediatric 
      cancer; it includes intensive multiagent chemotherapy and, often, hematopoietic 
      stem cell transplantation. Given the poor prognosis of pediatric AML and the 
      significant toxicity of standard AML therapy, novel therapies are needed. 
      Improved understanding of the molecular and cellular biology of leukemia has 
      facilitated the development of molecularly targeted therapies. In this article, 
      we review progress to date with agents that are showing promise in the treatment 
      of pediatric AML including targeted immunoconjugates, inhibitors of signaling 
      molecules (e.g. FMS-like tyrosine kinase 3 [FLT3], farnesyltransferase, and 
      mammalian target of rapamycin [mTOR]), agents that target epigenetic regulation 
      of gene expression (DNA methyltransferase inhibitors and histone deacetylase 
      inhibitors), and proteasome inhibitors. For the specific agents in each of these 
      classes, we summarize the published preclinical data and the clinical trials that 
      have been completed, are in progress, or are being planned for children with AML. 
      Finally, we discuss potential challenges to the success of molecularly targeted 
      therapy including demonstrating adequate targeting of leukemia stem cells, 
      developing synergistic and tolerable combinations of agents, and designing 
      adequately powered clinical trials to test efficacy in molecularly defined 
      subsets of patients.
FAU - Brown, Patrick
AU  - Brown P
AD  - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns 
      Hopkins, Baltimore, Maryland, USA. pbrown2@jhmi.edu
FAU - Smith, Franklin O
AU  - Smith FO
LA  - eng
GR  - K23 CA111728/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Switzerland
TA  - Paediatr Drugs
JT  - Paediatric drugs
JID - 100883685
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.5.1.29 (Farnesyltranstransferase)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - DNA Methylation
MH  - Farnesyltranstransferase/antagonists & inhibitors
MH  - Gene Expression Regulation, Leukemic
MH  - Histone Deacetylase Inhibitors
MH  - Humans
MH  - *Leukemia, Myeloid, Acute/genetics/therapy
MH  - Pediatrics
MH  - Proteasome Inhibitors
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - fms-Like Tyrosine Kinase 3/antagonists & inhibitors
RF  - 92
EDAT- 2008/03/19 09:00
MHDA- 2008/08/09 09:00
CRDT- 2008/03/19 09:00
PHST- 2008/03/19 09:00 [pubmed]
PHST- 2008/08/09 09:00 [medline]
PHST- 2008/03/19 09:00 [entrez]
AID - 1023 [pii]
AID - 10.2165/00148581-200810020-00003 [doi]
PST - ppublish
SO  - Paediatr Drugs. 2008;10(2):85-92. doi: 10.2165/00148581-200810020-00003.