FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2097773105> ?p ?o ?g. }

• W2097773105 endingPage "6986" @default.
• W2097773105 startingPage "6976" @default.
• W2097773105 abstract "Abstract Purpose: The oncogenic PI3K/Akt/mTOR pathway is an attractive therapeutic target in cancer. However, it is unknown whether the pathway blockade required for tumor growth inhibition is clinically achievable. Therefore, we conducted pharmacodynamic studies with GDC-0068, an ATP competitive, selective Akt1/2/3 inhibitor, in preclinical models and in patients treated with this compound. Experimental Design: We used a reverse phase protein array (RPPA) platform to identify a biomarker set indicative of Akt inhibition in cell lines and human-tumor xenografts, and correlated the degree of pathway inhibition with antitumor activity. Akt pathway activity was measured using this biomarker set in pre- and post-dose tumor biopsies from patients treated with GDC-0068 in the dose escalation clinical trial. Results: The set of biomarkers of Akt inhibition is composed of 10 phosphoproteins, including Akt and PRAS40, and is modulated in a dose-dependent fashion, both in vitro and in vivo. In human-tumor xenografts, this dose dependency significantly correlated with tumor growth inhibition. Tumor biopsies from patients treated with GDC-0068 at clinically achievable doses attained a degree of biomarker inhibition that correlated with tumor growth inhibition in preclinical models. In these clinical samples, compensatory feedback activation of ERK and HER3 was observed, consistent with preclinical observations. Conclusion: This study identified a set of biomarkers of Akt inhibition that can be used in the clinical setting to assess target engagement. Here, it was used to show that robust Akt inhibition in tumors from patients treated with GDC-0068 is achievable, supporting the clinical development of this compound in defined patient populations. Clin Cancer Res; 19(24); 6976–86. ©2013 AACR." @default.
• W2097773105 created "2016-06-24" @default.
• W2097773105 creator A5001032099 @default.
• W2097773105 creator A5002819777 @default.
• W2097773105 creator A5004300577 @default.
• W2097773105 creator A5015190461 @default.
• W2097773105 creator A5015761216 @default.
• W2097773105 creator A5016284879 @default.
• W2097773105 creator A5018105485 @default.
• W2097773105 creator A5021062064 @default.
• W2097773105 creator A5024623701 @default.
• W2097773105 creator A5036608249 @default.
• W2097773105 creator A5037266029 @default.
• W2097773105 creator A5047370165 @default.
• W2097773105 creator A5050390394 @default.
• W2097773105 creator A5057337648 @default.
• W2097773105 creator A5061081453 @default.
• W2097773105 creator A5069485042 @default.
• W2097773105 creator A5073423716 @default.
• W2097773105 creator A5078473824 @default.
• W2097773105 creator A5081998519 @default.
• W2097773105 creator A5082195410 @default.
• W2097773105 creator A5085170830 @default.
• W2097773105 creator A5091727687 @default.
• W2097773105 date "2013-12-15" @default.
• W2097773105 modified "2023-10-11" @default.
• W2097773105 title "Evaluation and Clinical Analyses of Downstream Targets of the Akt Inhibitor GDC-0068" @default.
• W2097773105 cites W1487234933 @default.
• W2097773105 cites W1966937303 @default.
• W2097773105 cites W1984621921 @default.
• W2097773105 cites W1990484467 @default.
• W2097773105 cites W2001208964 @default.
• W2097773105 cites W2015512041 @default.
• W2097773105 cites W2020372547 @default.
• W2097773105 cites W2026842712 @default.
• W2097773105 cites W2036450767 @default.
• W2097773105 cites W2052720710 @default.
• W2097773105 cites W2059411043 @default.
• W2097773105 cites W2060549297 @default.
• W2097773105 cites W2073414549 @default.
• W2097773105 cites W2077223675 @default.
• W2097773105 cites W2100490225 @default.
• W2097773105 cites W2119754956 @default.
• W2097773105 cites W2126783165 @default.
• W2097773105 cites W2134831715 @default.
• W2097773105 cites W2148541040 @default.
• W2097773105 cites W2155228605 @default.
• W2097773105 cites W2161422104 @default.
• W2097773105 cites W2161861008 @default.
• W2097773105 cites W2162409477 @default.
• W2097773105 cites W2166875189 @default.
• W2097773105 cites W2168037598 @default.
• W2097773105 cites W2257833854 @default.
• W2097773105 cites W2273740586 @default.
• W2097773105 cites W2590651193 @default.
• W2097773105 cites W3012056059 @default.
• W2097773105 cites W3012130451 @default.
• W2097773105 cites W4235501371 @default.
• W2097773105 doi "https://doi.org/10.1158/1078-0432.ccr-13-0978" @default.
• W2097773105 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24141624" @default.
• W2097773105 hasPublicationYear "2013" @default.
• W2097773105 type Work @default.
• W2097773105 sameAs 2097773105 @default.
• W2097773105 citedByCount "67" @default.
• W2097773105 countsByYear W20977731052014 @default.
• W2097773105 countsByYear W20977731052015 @default.
• W2097773105 countsByYear W20977731052016 @default.
• W2097773105 countsByYear W20977731052017 @default.
• W2097773105 countsByYear W20977731052018 @default.
• W2097773105 countsByYear W20977731052019 @default.
• W2097773105 countsByYear W20977731052020 @default.
• W2097773105 countsByYear W20977731052021 @default.
• W2097773105 countsByYear W20977731052022 @default.
• W2097773105 countsByYear W20977731052023 @default.
• W2097773105 crossrefType "journal-article" @default.
• W2097773105 hasAuthorship W2097773105A5001032099 @default.
• W2097773105 hasAuthorship W2097773105A5002819777 @default.
• W2097773105 hasAuthorship W2097773105A5004300577 @default.
• W2097773105 hasAuthorship W2097773105A5015190461 @default.
• W2097773105 hasAuthorship W2097773105A5015761216 @default.
• W2097773105 hasAuthorship W2097773105A5016284879 @default.
• W2097773105 hasAuthorship W2097773105A5018105485 @default.
• W2097773105 hasAuthorship W2097773105A5021062064 @default.
• W2097773105 hasAuthorship W2097773105A5024623701 @default.
• W2097773105 hasAuthorship W2097773105A5036608249 @default.
• W2097773105 hasAuthorship W2097773105A5037266029 @default.
• W2097773105 hasAuthorship W2097773105A5047370165 @default.
• W2097773105 hasAuthorship W2097773105A5050390394 @default.
• W2097773105 hasAuthorship W2097773105A5057337648 @default.
• W2097773105 hasAuthorship W2097773105A5061081453 @default.
• W2097773105 hasAuthorship W2097773105A5069485042 @default.
• W2097773105 hasAuthorship W2097773105A5073423716 @default.
• W2097773105 hasAuthorship W2097773105A5078473824 @default.
• W2097773105 hasAuthorship W2097773105A5081998519 @default.
• W2097773105 hasAuthorship W2097773105A5082195410 @default.
• W2097773105 hasAuthorship W2097773105A5085170830 @default.
• W2097773105 hasAuthorship W2097773105A5091727687 @default.
• W2097773105 hasBestOaLocation W20977731051 @default.

• next