Matches in SemOpenAlex for { <https://semopenalex.org/work/W2022309076> ?p ?o ?g. }
- W2022309076 endingPage "517" @default.
- W2022309076 startingPage "505" @default.
- W2022309076 abstract "Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in DNA repair. PARP inhibitors can act as chemosensitizers, or operate on the principle of synthetic lethality when used as single agent. Clinical trials have shown drugs in this class to be promising for BRCA mutation carriers. We postulated that inability to demonstrate response in non-BRCA carriers in which BRCA is inactivated by other mechanisms or with deficiency in homologous recombination for DNA repair is due to lack of molecular markers that define a responding subpopulation. We identified candidate markers for this purpose for olaparib (AstraZeneca) by measuring inhibitory effects of nine concentrations of olaparib in 22 breast cancer cell lines and identifying features in transcriptional and genome copy number profiles that were significantly correlated with response. We emphasized in this discovery process genes involved in DNA repair. We found that the cell lines that were sensitive to olaparib had a significant lower copy number of BRCA1 compared to the resistant cell lines (p value 0.012). In addition, we discovered seven genes from DNA repair pathways whose transcriptional levels were associated with response. These included five genes (BRCA1, MRE11A, NBS1, TDG, and XPA) whose transcript levels were associated with resistance and two genes (CHEK2 and MK2) whose transcript levels were associated with sensitivity. We developed an algorithm to predict response using the seven-gene transcription levels and applied it to 1,846 invasive breast cancer samples from 8 U133A/plus 2 (Affymetrix) data sets and found that 8–21 % of patients would be predicted to be responsive to olaparib. A similar response frequency was predicted in 536 samples analyzed on an Agilent platform. Importantly, tumors predicted to respond were enriched in basal subtype tumors. Our studies support clinical evaluation of the utility of our seven-gene signature as a predictor of response to olaparib." @default.
- W2022309076 created "2016-06-24" @default.
- W2022309076 creator A5005988887 @default.
- W2022309076 creator A5009616281 @default.
- W2022309076 creator A5018587370 @default.
- W2022309076 creator A5021847673 @default.
- W2022309076 creator A5022839853 @default.
- W2022309076 creator A5028899187 @default.
- W2022309076 creator A5029859470 @default.
- W2022309076 creator A5036890758 @default.
- W2022309076 creator A5038157510 @default.
- W2022309076 creator A5040450413 @default.
- W2022309076 creator A5044658654 @default.
- W2022309076 creator A5057324933 @default.
- W2022309076 creator A5058973407 @default.
- W2022309076 creator A5063399929 @default.
- W2022309076 creator A5077235697 @default.
- W2022309076 date "2012-08-09" @default.
- W2022309076 modified "2023-10-18" @default.
- W2022309076 title "Cross-platform pathway-based analysis identifies markers of response to the PARP inhibitor olaparib" @default.
- W2022309076 cites W1523531555 @default.
- W2022309076 cites W1656708631 @default.
- W2022309076 cites W1966182052 @default.
- W2022309076 cites W1969458729 @default.
- W2022309076 cites W1973268287 @default.
- W2022309076 cites W1977491006 @default.
- W2022309076 cites W1981191944 @default.
- W2022309076 cites W1981844581 @default.
- W2022309076 cites W1989643385 @default.
- W2022309076 cites W2009007206 @default.
- W2022309076 cites W2012346684 @default.
- W2022309076 cites W2036496759 @default.
- W2022309076 cites W2037867164 @default.
- W2022309076 cites W2038712263 @default.
- W2022309076 cites W2042181420 @default.
- W2022309076 cites W2044475740 @default.
- W2022309076 cites W2045164971 @default.
- W2022309076 cites W2050086663 @default.
- W2022309076 cites W2054929931 @default.
- W2022309076 cites W2062568878 @default.
- W2022309076 cites W2065849886 @default.
- W2022309076 cites W2077436902 @default.
- W2022309076 cites W2081562657 @default.
- W2022309076 cites W2081673104 @default.
- W2022309076 cites W2086038769 @default.
- W2022309076 cites W2099710128 @default.
- W2022309076 cites W2102752109 @default.
- W2022309076 cites W2102991803 @default.
- W2022309076 cites W2103272465 @default.
- W2022309076 cites W2105336633 @default.
- W2022309076 cites W2109001339 @default.
- W2022309076 cites W2116005493 @default.
- W2022309076 cites W2117964602 @default.
- W2022309076 cites W2118750229 @default.
- W2022309076 cites W2119767536 @default.
- W2022309076 cites W2120000242 @default.
- W2022309076 cites W2126983941 @default.
- W2022309076 cites W2127765486 @default.
- W2022309076 cites W2135195813 @default.
- W2022309076 cites W2135721953 @default.
- W2022309076 cites W2142658272 @default.
- W2022309076 cites W2142739240 @default.
- W2022309076 cites W2147908679 @default.
- W2022309076 cites W2157962151 @default.
- W2022309076 cites W2158501247 @default.
- W2022309076 cites W2161405893 @default.
- W2022309076 cites W2162946128 @default.
- W2022309076 cites W2171437346 @default.
- W2022309076 cites W2171806736 @default.
- W2022309076 cites W2171972386 @default.
- W2022309076 cites W2560160813 @default.
- W2022309076 cites W3093265161 @default.
- W2022309076 cites W3191675126 @default.
- W2022309076 doi "https://doi.org/10.1007/s10549-012-2188-0" @default.
- W2022309076 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3429780" @default.
- W2022309076 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22875744" @default.
- W2022309076 hasPublicationYear "2012" @default.
- W2022309076 type Work @default.
- W2022309076 sameAs 2022309076 @default.
- W2022309076 citedByCount "65" @default.
- W2022309076 countsByYear W20223090762013 @default.
- W2022309076 countsByYear W20223090762014 @default.
- W2022309076 countsByYear W20223090762015 @default.
- W2022309076 countsByYear W20223090762016 @default.
- W2022309076 countsByYear W20223090762017 @default.
- W2022309076 countsByYear W20223090762018 @default.
- W2022309076 countsByYear W20223090762019 @default.
- W2022309076 countsByYear W20223090762020 @default.
- W2022309076 countsByYear W20223090762021 @default.
- W2022309076 countsByYear W20223090762022 @default.
- W2022309076 countsByYear W20223090762023 @default.
- W2022309076 crossrefType "journal-article" @default.
- W2022309076 hasAuthorship W2022309076A5005988887 @default.
- W2022309076 hasAuthorship W2022309076A5009616281 @default.
- W2022309076 hasAuthorship W2022309076A5018587370 @default.
- W2022309076 hasAuthorship W2022309076A5021847673 @default.
- W2022309076 hasAuthorship W2022309076A5022839853 @default.
- W2022309076 hasAuthorship W2022309076A5028899187 @default.