PMID- 19519382
OWN - NLM
STAT- MEDLINE
DCOM- 20090803
LR  - 20220321
IS  - 0929-8673 (Print)
IS  - 0929-8673 (Linking)
VI  - 16
IP  - 17
DP  - 2009
TI  - Development of DNA methyltransferase inhibitors for the treatment of neoplastic 
      diseases.
PG  - 2075-85
AB  - Although chemotherapy is considered the mainstay of cancer therapy, unfortunate 
      side effects of chemotherapy create a continuous demand for developing other 
      novel and specific targets for cancer therapy. Re-expression of epigenetically 
      silenced tumor suppressor genes is a rational strategy for the treatment of human 
      neoplasms. Epigenetic modifiers like DNA methyltransferase (DNMT) inhibitors and 
      histone deacteylase (HDAC) inhibitors induce the re-expression of epigenetically 
      silenced genes in vitro and in vivo. Moreover, they demonstrate safety and 
      efficacy against neoplastic diseases in clinical trials. DNMT inhibitors like 
      5-azacytidine and 5-aza-2'-deoxycytidine are currently FDA approved for the 
      treatment of myelodysplastic syndrome. Nonetheless, the mechanism of action 
      behind their clinical efficacy remains unclear. Ongoing clinical trials are 
      attempting to identify tumor suppressor genes that upon re-expression can induce 
      remission and cure in patients. On the other hand, the pleiotropic biological 
      effects of DNMT inhibitors and recent reports demonstrating lack of association 
      between clinical response and methylation reversal of candidate tumor suppressor 
      genes, suggest a complex mechanism behind their clinical efficacy that may 
      involve a cytotoxic effect.
FAU - Fandy, Tamer E
AU  - Fandy TE
AD  - The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 
      Baltimore, MD 21231, USA. tfandy@jhu.edu
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/pharmacology/*therapeutic use
MH  - Clinical Trials as Topic
MH  - DNA (Cytosine-5-)-Methyltransferase 1
MH  - DNA (Cytosine-5-)-Methyltransferases/*antagonists & inhibitors/genetics
MH  - DNA Methylation/drug effects/genetics
MH  - Drug Design
MH  - Enzyme Inhibitors/chemistry/pharmacology/*therapeutic use
MH  - Epigenesis, Genetic/drug effects
MH  - Histone Deacetylase Inhibitors
MH  - Histone Deacetylases/genetics
MH  - Humans
MH  - Molecular Structure
MH  - Neoplasms/*drug therapy/enzymology/genetics
RF  - 105
EDAT- 2009/06/13 09:00
MHDA- 2009/08/04 09:00
CRDT- 2009/06/13 09:00
PHST- 2009/06/13 09:00 [entrez]
PHST- 2009/06/13 09:00 [pubmed]
PHST- 2009/08/04 09:00 [medline]
AID - 10.2174/092986709788612738 [doi]
PST - ppublish
SO  - Curr Med Chem. 2009;16(17):2075-85. doi: 10.2174/092986709788612738.