FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2810588143> ?p ?o ?g. }

• W2810588143 endingPage "321" @default.
• W2810588143 startingPage "321" @default.
• W2810588143 abstract "Abstract The DNA damage response (DDR) system consists of complex signalling pathways that secure the integrity of the genome in eukaryotic cells. DDR pathway activation follows recognition of DNA damage and results in cell cycle arrest, suppression of general translation, induction of DNA repair, cell survival or even cell death. Proteins that directly recognize aberrant DNA structures recruit and activate kinases of the DDR, such as ATR (ataxia telangiectasia and Rad3-related). ATR responds to a broad spectrum of DNA damages, including double-strand breaks (DSB) and lesions derived from interference with DNA replication as well as increased replication stress. Therefore, inhibition of ATR kinase activity could be the basis for a novel anti-cancer therapy in tumors with increased DNA damage, deficiency in DDR or replication stress. The potential of combining ATR kinase inhibitor with DNA damage inducing or DNA repair compromising anti-cancer therapeutics was studied in preclinical tumor models. We assessed the novel ATR kinase inhibitor (ATRi) BAY 1895344 in combination with external beam radiation therapy (EBRT), poly ADP ribose polymerase (PARP) inhibition or anti-androgen (AA) therapy. In cellular anti-proliferation assays as well as in tumor xenograft studies we could demonstrate synergistic activity of BAY 1895344 in combination treatment with the PARP inhibitor AZD-2281 in the homologous recombination (HR) defective breast cancer model MDA-MB-436, and with the non-steroidal AA darolutamide in the hormone-dependent prostate cancer model LAPC-4. Strong synergistic anti-tumor activity of BAY 1895344 could be further demonstrated in combination with EBRT inducing long-lasting tumor growth inhibition in the colorectal cancer xenograft model LOVO. The mechanism-based potential of combining DNA damage induction by EBRT with ATRi BAY 1895344 suggests a potential new treatment option for radiation therapy-resistant patients. Furthermore, the inhibition of parallel DDR pathways, as a combination of ATRi BAY 1895344 with a PARP inhibitor, indicates novel treatment opportunities in breast cancer patients with homologous recombination deficiencies, as does the synergism of BAY 1895344 and AA darolutamide therapy in hormone-dependent prostate cancer patients. BAY 1895344 is currently under clinical investigation in patients with advanced solid tumors and lymphomas (NCT03188965). Citation Format: Antje Margret Wengner, Gerhard Siemeister, Ulrich Luecking, Julien Lefranc, Kirstin Meyer, Eleni Lagkadinou, Bernard Haendler, Pascale Lejeune, Dominik Mumberg. Synergistic activity of the ATR inhibitor BAY 1895344 in combination with DNA damage inducing and DNA repair compromising therapies in preclinical tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 321." @default.
• W2810588143 created "2018-07-10" @default.
• W2810588143 creator A5009359386 @default.
• W2810588143 creator A5040107084 @default.
• W2810588143 creator A5045004231 @default.
• W2810588143 creator A5046614767 @default.
• W2810588143 creator A5048300451 @default.
• W2810588143 creator A5051447341 @default.
• W2810588143 creator A5064749364 @default.
• W2810588143 creator A5073018144 @default.
• W2810588143 creator A5085689791 @default.
• W2810588143 date "2018-07-01" @default.
• W2810588143 modified "2023-09-24" @default.
• W2810588143 title "Abstract 321: Synergistic activity of the ATR inhibitor BAY 1895344 in combination with DNA damage inducing and DNA repair compromising therapies in preclinical tumor models" @default.
• W2810588143 doi "https://doi.org/10.1158/1538-7445.am2018-321" @default.
• W2810588143 hasPublicationYear "2018" @default.
• W2810588143 type Work @default.
• W2810588143 sameAs 2810588143 @default.
• W2810588143 citedByCount "3" @default.
• W2810588143 countsByYear W28105881432020 @default.
• W2810588143 countsByYear W28105881432021 @default.
• W2810588143 crossrefType "journal-article" @default.
• W2810588143 hasAuthorship W2810588143A5009359386 @default.
• W2810588143 hasAuthorship W2810588143A5040107084 @default.
• W2810588143 hasAuthorship W2810588143A5045004231 @default.
• W2810588143 hasAuthorship W2810588143A5046614767 @default.
• W2810588143 hasAuthorship W2810588143A5048300451 @default.
• W2810588143 hasAuthorship W2810588143A5051447341 @default.
• W2810588143 hasAuthorship W2810588143A5064749364 @default.
• W2810588143 hasAuthorship W2810588143A5073018144 @default.
• W2810588143 hasAuthorship W2810588143A5085689791 @default.
• W2810588143 hasConcept C105696609 @default.
• W2810588143 hasConcept C121608353 @default.
• W2810588143 hasConcept C134935766 @default.
• W2810588143 hasConcept C143425029 @default.
• W2810588143 hasConcept C153911025 @default.
• W2810588143 hasConcept C178169997 @default.
• W2810588143 hasConcept C182979987 @default.
• W2810588143 hasConcept C184235292 @default.
• W2810588143 hasConcept C185592680 @default.
• W2810588143 hasConcept C2779138821 @default.
• W2810588143 hasConcept C29537977 @default.
• W2810588143 hasConcept C50001416 @default.
• W2810588143 hasConcept C502942594 @default.
• W2810588143 hasConcept C54355233 @default.
• W2810588143 hasConcept C552990157 @default.
• W2810588143 hasConcept C82381507 @default.
• W2810588143 hasConcept C86803240 @default.
• W2810588143 hasConcept C95444343 @default.
• W2810588143 hasConceptScore W2810588143C105696609 @default.
• W2810588143 hasConceptScore W2810588143C121608353 @default.
• W2810588143 hasConceptScore W2810588143C134935766 @default.
• W2810588143 hasConceptScore W2810588143C143425029 @default.
• W2810588143 hasConceptScore W2810588143C153911025 @default.
• W2810588143 hasConceptScore W2810588143C178169997 @default.
• W2810588143 hasConceptScore W2810588143C182979987 @default.
• W2810588143 hasConceptScore W2810588143C184235292 @default.
• W2810588143 hasConceptScore W2810588143C185592680 @default.
• W2810588143 hasConceptScore W2810588143C2779138821 @default.
• W2810588143 hasConceptScore W2810588143C29537977 @default.
• W2810588143 hasConceptScore W2810588143C50001416 @default.
• W2810588143 hasConceptScore W2810588143C502942594 @default.
• W2810588143 hasConceptScore W2810588143C54355233 @default.
• W2810588143 hasConceptScore W2810588143C552990157 @default.
• W2810588143 hasConceptScore W2810588143C82381507 @default.
• W2810588143 hasConceptScore W2810588143C86803240 @default.
• W2810588143 hasConceptScore W2810588143C95444343 @default.
• W2810588143 hasIssue "13_Supplement" @default.
• W2810588143 hasLocation W28105881431 @default.
• W2810588143 hasOpenAccess W2810588143 @default.
• W2810588143 hasPrimaryLocation W28105881431 @default.
• W2810588143 hasRelatedWork W1553367038 @default.
• W2810588143 hasRelatedWork W1809005416 @default.
• W2810588143 hasRelatedWork W1980460135 @default.
• W2810588143 hasRelatedWork W2004103693 @default.
• W2810588143 hasRelatedWork W2043680807 @default.
• W2810588143 hasRelatedWork W2745136073 @default.
• W2810588143 hasRelatedWork W2801224314 @default.
• W2810588143 hasRelatedWork W2810299524 @default.
• W2810588143 hasRelatedWork W2810588143 @default.
• W2810588143 hasRelatedWork W3044867089 @default.
• W2810588143 hasVolume "78" @default.
• W2810588143 isParatext "false" @default.
• W2810588143 isRetracted "false" @default.
• W2810588143 magId "2810588143" @default.
• W2810588143 workType "article" @default.