FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2950950009> ?p ?o ?g. }

• W2950950009 endingPage "5594" @default.
• W2950950009 startingPage "5584" @default.
• W2950950009 abstract "Abstract Purpose: Somatic inactivating mutations in ARID1A, a component of the SWI/SNF chromatin remodeling complex, are detected in various types of human malignancies. Loss of ARID1A compromises DNA damage repair. The induced DNA damage burden may increase reliance on PARP-dependent DNA repair of cancer cells to maintain genome integrity and render susceptibility to PARP inhibitor therapy. Experimental Design: Isogenic ARID1A−/− and wild-type cell lines were used for assessing DNA damage response, DNA compactness, and profiling global serine/threonine phosphoproteomic in vivo. A panel of inhibitors targeting DNA repair pathways was screened for a synergistic antitumor effect with irradiation in ARID1A−/− tumors. Results: ARID1A-deficient endometrial cells exhibit sustained levels in DNA damage response, a result further supported by in vivo phosphoproteomic analysis. Our results show that ARID1A is essential for establishing an open chromatin state upon DNA damage, a process required for recruitment of 53BP1 and RIF1, key mediators of non-homologous end-joining (NHEJ) machinery, to DNA lesions. The inability of ARID1A−/− cells to mount NHEJ repair results in a partial cytotoxic response to radiation. Small-molecule compound screens revealed that PARP inhibitors act synergistically with radiation to potentiate cytotoxicity in ARID1A−/− cells. Combination treatment with low-dose radiation and olaparib greatly improved antitumor efficacy, resulting in long-term remission in mice bearing ARID1A-deficient tumors. Conclusions: ARID1A-deficient cells acquire high sensitivity to PARP inhibition after exposure to exogenously induced DNA breaks such as ionizing radiation. Our findings suggest a novel biologically informed strategy for treating ARID1A-deficient malignancies." @default.
• W2950950009 created "2019-06-27" @default.
• W2950950009 creator A5008193447 @default.
• W2950950009 creator A5014887786 @default.
• W2950950009 creator A5015952679 @default.
• W2950950009 creator A5019250137 @default.
• W2950950009 creator A5022089118 @default.
• W2950950009 creator A5031348375 @default.
• W2950950009 creator A5033744514 @default.
• W2950950009 creator A5034117446 @default.
• W2950950009 creator A5036550290 @default.
• W2950950009 creator A5041445051 @default.
• W2950950009 creator A5053471314 @default.
• W2950950009 creator A5054660253 @default.
• W2950950009 creator A5078762063 @default.
• W2950950009 creator A5089917586 @default.
• W2950950009 creator A5091274044 @default.
• W2950950009 date "2019-09-13" @default.
• W2950950009 modified "2023-10-11" @default.
• W2950950009 title "Loss of ARID1A in Tumor Cells Renders Selective Vulnerability to Combined Ionizing Radiation and PARP Inhibitor Therapy" @default.
• W2950950009 cites W1825010762 @default.
• W2950950009 cites W1975141727 @default.
• W2950950009 cites W1975307022 @default.
• W2950950009 cites W1978088642 @default.
• W2950950009 cites W1991396678 @default.
• W2950950009 cites W2007369689 @default.
• W2950950009 cites W2013107316 @default.
• W2950950009 cites W2018851752 @default.
• W2950950009 cites W2019025864 @default.
• W2950950009 cites W2020091112 @default.
• W2950950009 cites W2022093187 @default.
• W2950950009 cites W2034852369 @default.
• W2950950009 cites W2039189450 @default.
• W2950950009 cites W2041440766 @default.
• W2950950009 cites W2047664934 @default.
• W2950950009 cites W2056946030 @default.
• W2950950009 cites W2058836507 @default.
• W2950950009 cites W2068275655 @default.
• W2950950009 cites W2068523052 @default.
• W2950950009 cites W2075053675 @default.
• W2950950009 cites W2086775982 @default.
• W2950950009 cites W2090704952 @default.
• W2950950009 cites W2093814864 @default.
• W2950950009 cites W2096439168 @default.
• W2950950009 cites W2098737737 @default.
• W2950950009 cites W2100871132 @default.
• W2950950009 cites W2123454509 @default.
• W2950950009 cites W2145583284 @default.
• W2950950009 cites W2170768661 @default.
• W2950950009 cites W2171972386 @default.
• W2950950009 cites W2179093278 @default.
• W2950950009 cites W2285093314 @default.
• W2950950009 cites W2293749183 @default.
• W2950950009 cites W2382242955 @default.
• W2950950009 cites W2507112541 @default.
• W2950950009 cites W2531736191 @default.
• W2950950009 cites W2621502270 @default.
• W2950950009 cites W2747616390 @default.
• W2950950009 cites W2773508959 @default.
• W2950950009 doi "https://doi.org/10.1158/1078-0432.ccr-18-4222" @default.
• W2950950009 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7272114" @default.
• W2950950009 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31196855" @default.
• W2950950009 hasPublicationYear "2019" @default.
• W2950950009 type Work @default.
• W2950950009 sameAs 2950950009 @default.
• W2950950009 citedByCount "70" @default.
• W2950950009 countsByYear W29509500092019 @default.
• W2950950009 countsByYear W29509500092020 @default.
• W2950950009 countsByYear W29509500092021 @default.
• W2950950009 countsByYear W29509500092022 @default.
• W2950950009 countsByYear W29509500092023 @default.
• W2950950009 crossrefType "journal-article" @default.
• W2950950009 hasAuthorship W2950950009A5008193447 @default.
• W2950950009 hasAuthorship W2950950009A5014887786 @default.
• W2950950009 hasAuthorship W2950950009A5015952679 @default.
• W2950950009 hasAuthorship W2950950009A5019250137 @default.
• W2950950009 hasAuthorship W2950950009A5022089118 @default.
• W2950950009 hasAuthorship W2950950009A5031348375 @default.
• W2950950009 hasAuthorship W2950950009A5033744514 @default.
• W2950950009 hasAuthorship W2950950009A5034117446 @default.
• W2950950009 hasAuthorship W2950950009A5036550290 @default.
• W2950950009 hasAuthorship W2950950009A5041445051 @default.
• W2950950009 hasAuthorship W2950950009A5053471314 @default.
• W2950950009 hasAuthorship W2950950009A5054660253 @default.
• W2950950009 hasAuthorship W2950950009A5078762063 @default.
• W2950950009 hasAuthorship W2950950009A5089917586 @default.
• W2950950009 hasAuthorship W2950950009A5091274044 @default.
• W2950950009 hasBestOaLocation W29509500091 @default.
• W2950950009 hasConcept C104317684 @default.
• W2950950009 hasConcept C134935766 @default.
• W2950950009 hasConcept C143425029 @default.
• W2950950009 hasConcept C182979987 @default.
• W2950950009 hasConcept C2779138821 @default.
• W2950950009 hasConcept C2779962180 @default.
• W2950950009 hasConcept C2781273526 @default.
• W2950950009 hasConcept C501734568 @default.
• W2950950009 hasConcept C502942594 @default.
• W2950950009 hasConcept C54355233 @default.

• next