FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3043267144> ?p ?o ?g. }

• W3043267144 abstract "ABSTRACT The majority of metastatic, castrate-resistant prostate cancer (mCRPC) patients are de novo resistant to immune checkpoint blockade (ICB), so therapeutic strategies to enhance immune-responsiveness are urgently needed. Here we performed a co-clinical trial of PARP inhibitor (PARPi) in combination with PD-1 or PDL-1 antibody in genomically unselected mCRPC patients or homologous-recombination proficient murine models, respectively, which demonstrated lack of efficacy. In contrast, PARPi in combination with PI3K inhibitor (PI3Ki), induced tumor regression via macrophage STING-dependent innate immune activation in vivo , and enhanced T-cell infiltration/activation in c-myc driven murine prostate cancer models, which was augmented by PD-L1 blockade. Ex vivo mechanistic studies revealed that PARPi-induced DNA double strand break-associated microvesicles released from tumor cells, coupled with PI3Ki-mediated c-GAS de-repression, were both required for macrophage cGAS/STING pathway activation. These data demonstrate that PARPi/PI3Ki combination triggers macrophage STING-mediated anti-cancer innate immunity, which is sufficient to induce tumor regression in ICB-refractory c-myc-driven prostate cancer. STATEMENT OF SIGNIFICANCE Co-targeting of PARP and PI3K signaling pathways activates c-GAS/STING pathway within tumor-associated macrophages, thereby enhancing T cell recruitment/activation and cancer clearance in c-myc-driven murine prostate cancer models. PARPi/PI3Ki combination therapy could markedly increase the fraction of mCRPC patients responsive to ICB, independent of germline or tumor homologous recombination status." @default.
• W3043267144 created "2020-07-23" @default.
• W3043267144 creator A5003149806 @default.
• W3043267144 creator A5019657425 @default.
• W3043267144 creator A5035939498 @default.
• W3043267144 creator A5068014441 @default.
• W3043267144 creator A5069294979 @default.
• W3043267144 creator A5073680897 @default.
• W3043267144 creator A5081681820 @default.
• W3043267144 creator A5088131964 @default.
• W3043267144 date "2020-07-18" @default.
• W3043267144 modified "2023-10-17" @default.
• W3043267144 title "PARP and PI3K inhibitor combination therapy eradicates c-MYC-driven murine prostate cancers via cGAS/STING pathway activation within tumor-associated macrophages" @default.
• W3043267144 cites W1898887656 @default.
• W3043267144 cites W2056241473 @default.
• W3043267144 cites W2066586758 @default.
• W3043267144 cites W2120806256 @default.
• W3043267144 cites W2122158568 @default.
• W3043267144 cites W2142226776 @default.
• W3043267144 cites W2154171253 @default.
• W3043267144 cites W2160834915 @default.
• W3043267144 cites W2161227864 @default.
• W3043267144 cites W2169228223 @default.
• W3043267144 cites W2237797200 @default.
• W3043267144 cites W2401674736 @default.
• W3043267144 cites W2564433363 @default.
• W3043267144 cites W2587048937 @default.
• W3043267144 cites W2596947528 @default.
• W3043267144 cites W2607477299 @default.
• W3043267144 cites W2756577188 @default.
• W3043267144 cites W2766100101 @default.
• W3043267144 cites W2771976702 @default.
• W3043267144 cites W2795073885 @default.
• W3043267144 cites W2806421539 @default.
• W3043267144 cites W2807798312 @default.
• W3043267144 cites W2887329987 @default.
• W3043267144 cites W2887577080 @default.
• W3043267144 cites W2898817714 @default.
• W3043267144 cites W2902486285 @default.
• W3043267144 cites W2903718866 @default.
• W3043267144 cites W2907541282 @default.
• W3043267144 cites W2909513097 @default.
• W3043267144 cites W2942052760 @default.
• W3043267144 cites W2947826965 @default.
• W3043267144 cites W2954862062 @default.
• W3043267144 cites W2966904528 @default.
• W3043267144 cites W2967997773 @default.
• W3043267144 cites W2980322460 @default.
• W3043267144 cites W2989894179 @default.
• W3043267144 cites W2992135268 @default.
• W3043267144 cites W2999417355 @default.
• W3043267144 cites W3003351147 @default.
• W3043267144 cites W3004615009 @default.
• W3043267144 cites W3007445605 @default.
• W3043267144 cites W3008060424 @default.
• W3043267144 cites W3012105756 @default.
• W3043267144 cites W3014239680 @default.
• W3043267144 cites W3020771563 @default.
• W3043267144 doi "https://doi.org/10.1101/2020.07.17.198598" @default.
• W3043267144 hasPublicationYear "2020" @default.
• W3043267144 type Work @default.
• W3043267144 sameAs 3043267144 @default.
• W3043267144 citedByCount "3" @default.
• W3043267144 countsByYear W30432671442021 @default.
• W3043267144 countsByYear W30432671442022 @default.
• W3043267144 crossrefType "posted-content" @default.
• W3043267144 hasAuthorship W3043267144A5003149806 @default.
• W3043267144 hasAuthorship W3043267144A5019657425 @default.
• W3043267144 hasAuthorship W3043267144A5035939498 @default.
• W3043267144 hasAuthorship W3043267144A5068014441 @default.
• W3043267144 hasAuthorship W3043267144A5069294979 @default.
• W3043267144 hasAuthorship W3043267144A5073680897 @default.
• W3043267144 hasAuthorship W3043267144A5081681820 @default.
• W3043267144 hasAuthorship W3043267144A5088131964 @default.
• W3043267144 hasBestOaLocation W30432671441 @default.
• W3043267144 hasConcept C104317684 @default.
• W3043267144 hasConcept C121608353 @default.
• W3043267144 hasConcept C126322002 @default.
• W3043267144 hasConcept C136449434 @default.
• W3043267144 hasConcept C182979987 @default.
• W3043267144 hasConcept C203014093 @default.
• W3043267144 hasConcept C2777701055 @default.
• W3043267144 hasConcept C2779138821 @default.
• W3043267144 hasConcept C2780192828 @default.
• W3043267144 hasConcept C2780851360 @default.
• W3043267144 hasConcept C502942594 @default.
• W3043267144 hasConcept C55493867 @default.
• W3043267144 hasConcept C71924100 @default.
• W3043267144 hasConcept C82381507 @default.
• W3043267144 hasConcept C86803240 @default.
• W3043267144 hasConcept C8891405 @default.
• W3043267144 hasConceptScore W3043267144C104317684 @default.
• W3043267144 hasConceptScore W3043267144C121608353 @default.
• W3043267144 hasConceptScore W3043267144C126322002 @default.
• W3043267144 hasConceptScore W3043267144C136449434 @default.
• W3043267144 hasConceptScore W3043267144C182979987 @default.
• W3043267144 hasConceptScore W3043267144C203014093 @default.
• W3043267144 hasConceptScore W3043267144C2777701055 @default.
• W3043267144 hasConceptScore W3043267144C2779138821 @default.
• W3043267144 hasConceptScore W3043267144C2780192828 @default.

• next