Linked Life Data

20818418

Source:http://linkedlifedata.com/resource/pubmed/id/20818418

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2010-11-24
pubmed:abstractText
The DNA-damage response (DDR) pathways consist of interconnected components that respond to DNA damage to allow repair and promote cell survival. The DNA repair pathways and downstream cellular responses have diverged in cancer cells compared with normal cells because of genetic alterations that underlie drug resistance, disabled repair and resistance to apoptosis. Consequently, abrogating DDR pathways represents an important mechanism for enhancing the therapeutic index of DNA-damaging anticancer agents. In this review, we discuss the DDR pathways that determine antitumor effects of DNA-damaging agents with a specific focus on treatment outcomes in tumors carrying a defective p53 pathway. Finely tuned survival and death pathways govern the cellular responses downstream of the cytotoxic insults inherent in anticancer treatment. The significance and relative contributions of cellular responses including apoptosis, mitotic catastrophe and senescence are discussed in relation to the web of molecular interactions that affect such outcomes. We propose that promising combinations of DNA-damaging anticancer treatments with DDR-pathway inhibition would be further enhanced by activating downstream apoptotic pathways. The proposed rationale ensures that actual cell death is the preferred outcome of cancer treatment instead of other responses, including reversible cell cycle arrest, autophagy or senescence. Finally, to better measure the contribution of different cellular responses to anticancer treatments, multiplex in vivo assessments of therapy-induced response pathways such as cell death, senescence and mitotic catastrophe is desirable rather than the current reliance on the measurement of a single response pathway such as apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6085-98
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes.
pubmed:affiliation
Signal Transduction Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. Fares.Al-Ejeh@qimr.edu.au
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't