FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361946218> ?p ?o ?g. }

• W4361946218 abstract "<div>Abstract<p><b>Purpose:</b> Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high-throughput and mechanistic analysis.</p><p><b>Experimental Design:</b> Using 20 models from the LuCaP mCRPC PDX cohort, including adenocarcinoma and neuroendocrine lineages, we systematically tested >20 modifications to prostate organoid conditions. Organoids were evaluated for genomic and phenotypic stability and continued reliance on the AR signaling pathway. The utility of the platform as a genotype-dependent model of drug sensitivity was tested with olaparib and carboplatin.</p><p><b>Results:</b> All PDX models proliferated as organoids in culture. Greater than 50% could be continuously cultured long-term in modified conditions; however, none of the PDXs could be established long-term as organoids under previously reported conditions. In addition, the modified conditions improved the establishment of patient biopsies over current methods. The genomic heterogeneity of the PDXs was conserved in organoids. Lineage markers and transcriptomes were maintained between PDXs and organoids. Dependence on AR signaling was preserved in adenocarcinoma organoids, replicating a dominant characteristic of CRPC. Finally, we observed maximum cytotoxicity to the PARP inhibitor olaparib in <i>BRCA2</i>^−/− organoids, similar to responses observed in patients.</p><p><b>Conclusions:</b> The LuCaP PDX/organoid models provide an expansive, genetically characterized platform to investigate the mechanisms of pathogenesis as well as therapeutic responses and their molecular correlates in mCRPC. <i>Clin Cancer Res; 24(17); 4332–45. ©2018 AACR</i>.</p></div>" @default.
• W4361946218 created "2023-04-05" @default.
• W4361946218 creator A5002466627 @default.
• W4361946218 creator A5012084322 @default.
• W4361946218 creator A5015195078 @default.
• W4361946218 creator A5015713542 @default.
• W4361946218 creator A5018745405 @default.
• W4361946218 creator A5025720503 @default.
• W4361946218 creator A5027334479 @default.
• W4361946218 creator A5030186057 @default.
• W4361946218 creator A5039452787 @default.
• W4361946218 creator A5046002182 @default.
• W4361946218 creator A5062801846 @default.
• W4361946218 creator A5065550926 @default.
• W4361946218 creator A5083596371 @default.
• W4361946218 creator A5085115963 @default.
• W4361946218 creator A5085664221 @default.
• W4361946218 date "2023-03-31" @default.
• W4361946218 modified "2023-10-14" @default.
• W4361946218 title "Data from A PDX/Organoid Biobank of Advanced Prostate Cancers Captures Genomic and Phenotypic Heterogeneity for Disease Modeling and Therapeutic Screening" @default.
• W4361946218 doi "https://doi.org/10.1158/1078-0432.c.6527324" @default.
• W4361946218 hasPublicationYear "2023" @default.
• W4361946218 type Work @default.
• W4361946218 citedByCount "0" @default.
• W4361946218 crossrefType "posted-content" @default.
• W4361946218 hasAuthorship W4361946218A5002466627 @default.
• W4361946218 hasAuthorship W4361946218A5012084322 @default.
• W4361946218 hasAuthorship W4361946218A5015195078 @default.
• W4361946218 hasAuthorship W4361946218A5015713542 @default.
• W4361946218 hasAuthorship W4361946218A5018745405 @default.
• W4361946218 hasAuthorship W4361946218A5025720503 @default.
• W4361946218 hasAuthorship W4361946218A5027334479 @default.
• W4361946218 hasAuthorship W4361946218A5030186057 @default.
• W4361946218 hasAuthorship W4361946218A5039452787 @default.
• W4361946218 hasAuthorship W4361946218A5046002182 @default.
• W4361946218 hasAuthorship W4361946218A5062801846 @default.
• W4361946218 hasAuthorship W4361946218A5065550926 @default.
• W4361946218 hasAuthorship W4361946218A5083596371 @default.
• W4361946218 hasAuthorship W4361946218A5085115963 @default.
• W4361946218 hasAuthorship W4361946218A5085664221 @default.
• W4361946218 hasBestOaLocation W43619462182 @default.
• W4361946218 hasConcept C104317684 @default.
• W4361946218 hasConcept C116567970 @default.
• W4361946218 hasConcept C121608353 @default.
• W4361946218 hasConcept C126322002 @default.
• W4361946218 hasConcept C127716648 @default.
• W4361946218 hasConcept C150194340 @default.
• W4361946218 hasConcept C162317418 @default.
• W4361946218 hasConcept C182979987 @default.
• W4361946218 hasConcept C2779134260 @default.
• W4361946218 hasConcept C2779962180 @default.
• W4361946218 hasConcept C2780192828 @default.
• W4361946218 hasConcept C31695470 @default.
• W4361946218 hasConcept C32220436 @default.
• W4361946218 hasConcept C502942594 @default.
• W4361946218 hasConcept C54355233 @default.
• W4361946218 hasConcept C60644358 @default.
• W4361946218 hasConcept C71924100 @default.
• W4361946218 hasConcept C82381507 @default.
• W4361946218 hasConcept C86803240 @default.
• W4361946218 hasConceptScore W4361946218C104317684 @default.
• W4361946218 hasConceptScore W4361946218C116567970 @default.
• W4361946218 hasConceptScore W4361946218C121608353 @default.
• W4361946218 hasConceptScore W4361946218C126322002 @default.
• W4361946218 hasConceptScore W4361946218C127716648 @default.
• W4361946218 hasConceptScore W4361946218C150194340 @default.
• W4361946218 hasConceptScore W4361946218C162317418 @default.
• W4361946218 hasConceptScore W4361946218C182979987 @default.
• W4361946218 hasConceptScore W4361946218C2779134260 @default.
• W4361946218 hasConceptScore W4361946218C2779962180 @default.
• W4361946218 hasConceptScore W4361946218C2780192828 @default.
• W4361946218 hasConceptScore W4361946218C31695470 @default.
• W4361946218 hasConceptScore W4361946218C32220436 @default.
• W4361946218 hasConceptScore W4361946218C502942594 @default.
• W4361946218 hasConceptScore W4361946218C54355233 @default.
• W4361946218 hasConceptScore W4361946218C60644358 @default.
• W4361946218 hasConceptScore W4361946218C71924100 @default.
• W4361946218 hasConceptScore W4361946218C82381507 @default.
• W4361946218 hasConceptScore W4361946218C86803240 @default.
• W4361946218 hasLocation W43619462181 @default.
• W4361946218 hasLocation W43619462182 @default.
• W4361946218 hasOpenAccess W4361946218 @default.
• W4361946218 hasPrimaryLocation W43619462181 @default.
• W4361946218 hasRelatedWork W1899936169 @default.
• W4361946218 hasRelatedWork W2896450660 @default.
• W4361946218 hasRelatedWork W3088242518 @default.
• W4361946218 hasRelatedWork W3200361252 @default.
• W4361946218 hasRelatedWork W4200451890 @default.
• W4361946218 hasRelatedWork W4303579080 @default.
• W4361946218 hasRelatedWork W4361946218 @default.
• W4361946218 hasRelatedWork W4361952775 @default.
• W4361946218 hasRelatedWork W2479526788 @default.
• W4361946218 hasRelatedWork W3142365251 @default.
• W4361946218 isParatext "false" @default.
• W4361946218 isRetracted "false" @default.
• W4361946218 workType "article" @default.