Linked Life Data

20976469

Source:http://linkedlifedata.com/resource/pubmed/id/20976469

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-11-12
pubmed:abstractText
Synthetic lethal interaction is defined as a combination of two mutations that is lethal when present in the same cell; each individual mutation is non-lethal. Synthetic lethal interactions attract attention in cancer research fields since the discovery of synthetic lethal genes with either oncogenes or tumor suppressor genes (TSGs) provides novel cancer therapeutic targets. Due to the selective lethal effect on cancer cells harboring specific genetic alterations, it is expected that targeting synthetic lethal genes would provide wider therapeutic windows compared with cytotoxic chemotherapeutics. Here, we review the current status of the application of synthetic lethal screening in cancer research fields from biological and methodological viewpoints. Very recent studies seeking to identify synthetic lethal genes with K-RAS and p53, which are known to be the most frequently occurring oncogenes and TSGs, respectively, are introduced. Among the accumulating amount of research on synthetic lethal interactions, the synthetic lethality between BRCA1/2 and PARP1 inhibition has been clinically proven. Thus, both preclinical and clinical data showing a preferential anti-tumor effect on BRCA1/2 deficient tumors by a PARP1 inhibitor are the best examples of the synthetic lethal approach of cancer therapeutics. Finally, methodological progress regarding synthetic lethal screening, including barcode shRNA screening and in vivo synthetic lethal screening, is described. Given the fact that an increasing number of synthetic lethal genes for major cancerous genes have been validated in preclinical studies, this intriguing approach awaits clinical verification of preferential benefits for cancer patients with specific genetic alterations as a clear predictive factor for tumor response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1432-1203
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
567-75
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Synthetic lethal interactions for the development of cancer therapeutics: biological and methodological advancements.
pubmed:affiliation
Department of Oncology, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki, 300-2611, Japan.
pubmed:publicationType
Journal Article, Review