Linked Life Data

20823146

Source:http://linkedlifedata.com/resource/pubmed/id/20823146

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2010-9-16
pubmed:abstractText
Tumor cells are often deficient in DNA damage response (DDR) pathways, and anticancer therapies are commonly based on genotoxic treatments using radiation and/or drugs that damage DNA directly or interfere with DNA metabolism, leading to the formation of DNA double-strand breaks (DSB), and ultimately to cell death. Because DSBs induce the phosphorylation of histone H2AX (?H2AX) in the chromatin flanking the break site, an antibody directed against ?H2AX can be employed to measure DNA damage levels before and after patient treatment. Poly(ADP-ribose) polymerases (PARP1 and PARP2) are also activated by DNA damage, and PARP inhibitors show promising activity in cancers with defective homologous recombination (HR) pathways for DSB repair. Ongoing clinical trials are testing combinations of PARP inhibitors with DNA damaging agents. Poly(ADP-ribosylation), abbreviated as PAR, can be measured in clinical samples and used to determine the efficiency of PARP inhibitors. This review summarizes the roles of ?H2AX and PAR in the DDR, and their use as biomarkers to monitor drug response and guide clinical trials, especially phase 0 clinical trials. We also discuss the choices of relevant samples for ?H2AX and PAR analyses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1078-0432
pubmed:author
pubmed:copyrightInfo
©2010 AACR.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4532-42
pubmed:dateRevised
2011-9-19
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Histone gammaH2AX and poly(ADP-ribose) as clinical pharmacodynamic biomarkers.
pubmed:affiliation
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Review, Evaluation Studies, Research Support, N.I.H., Intramural