Matches in SemOpenAlex for { <https://semopenalex.org/work/W2905058646> ?p ?o ?g. }
- W2905058646 endingPage "938.e7" @default.
- W2905058646 startingPage "922" @default.
- W2905058646 abstract "Drug resistance represents a major challenge to achieving durable responses to cancer therapeutics. Resistance mechanisms to epigenetically targeted drugs remain largely unexplored. We used bromodomain and extra-terminal domain (BET) inhibition in neuroblastoma as a prototype to model resistance to chromatin modulatory therapeutics. Genome-scale, pooled lentiviral open reading frame (ORF) and CRISPR knockout rescue screens nominated the phosphatidylinositol 3-kinase (PI3K) pathway as promoting resistance to BET inhibition. Transcriptomic and chromatin profiling of resistant cells revealed that global enhancer remodeling is associated with upregulation of receptor tyrosine kinases (RTKs), activation of PI3K signaling, and vulnerability to RTK/PI3K inhibition. Large-scale combinatorial screening with BET inhibitors identified PI3K inhibitors among the most synergistic upfront combinations. These studies provide a roadmap to elucidate resistance to epigenetic-targeted therapeutics and inform efficacious combination therapies." @default.
- W2905058646 created "2018-12-22" @default.
- W2905058646 creator A5005268578 @default.
- W2905058646 creator A5008226128 @default.
- W2905058646 creator A5009855916 @default.
- W2905058646 creator A5011524529 @default.
- W2905058646 creator A5011985711 @default.
- W2905058646 creator A5014371302 @default.
- W2905058646 creator A5015754037 @default.
- W2905058646 creator A5018167603 @default.
- W2905058646 creator A5019650465 @default.
- W2905058646 creator A5022484206 @default.
- W2905058646 creator A5022924056 @default.
- W2905058646 creator A5031035835 @default.
- W2905058646 creator A5031650279 @default.
- W2905058646 creator A5031962656 @default.
- W2905058646 creator A5035834075 @default.
- W2905058646 creator A5037413866 @default.
- W2905058646 creator A5041980697 @default.
- W2905058646 creator A5045161756 @default.
- W2905058646 creator A5045525984 @default.
- W2905058646 creator A5048549389 @default.
- W2905058646 creator A5060463684 @default.
- W2905058646 creator A5065933711 @default.
- W2905058646 creator A5069062997 @default.
- W2905058646 creator A5072926885 @default.
- W2905058646 creator A5073989912 @default.
- W2905058646 creator A5085626192 @default.
- W2905058646 date "2018-12-01" @default.
- W2905058646 modified "2023-10-17" @default.
- W2905058646 title "Resistance to Epigenetic-Targeted Therapy Engenders Tumor Cell Vulnerabilities Associated with Enhancer Remodeling" @default.
- W2905058646 cites W1915238740 @default.
- W2905058646 cites W1963740134 @default.
- W2905058646 cites W1969075054 @default.
- W2905058646 cites W1972301614 @default.
- W2905058646 cites W1976033223 @default.
- W2905058646 cites W1979594866 @default.
- W2905058646 cites W1990174038 @default.
- W2905058646 cites W1993186884 @default.
- W2905058646 cites W1996203485 @default.
- W2905058646 cites W2002162019 @default.
- W2905058646 cites W2009642188 @default.
- W2905058646 cites W2009720434 @default.
- W2905058646 cites W2009949436 @default.
- W2905058646 cites W2014677321 @default.
- W2905058646 cites W2015616444 @default.
- W2905058646 cites W2023994677 @default.
- W2905058646 cites W2030205108 @default.
- W2905058646 cites W2031211461 @default.
- W2905058646 cites W2032365395 @default.
- W2905058646 cites W2040575339 @default.
- W2905058646 cites W2041535798 @default.
- W2905058646 cites W2043148368 @default.
- W2905058646 cites W2060484997 @default.
- W2905058646 cites W2077945404 @default.
- W2905058646 cites W2079012552 @default.
- W2905058646 cites W2089941368 @default.
- W2905058646 cites W2093146349 @default.
- W2905058646 cites W2096439168 @default.
- W2905058646 cites W2103441770 @default.
- W2905058646 cites W2103562758 @default.
- W2905058646 cites W2104830962 @default.
- W2905058646 cites W2109378990 @default.
- W2905058646 cites W2110444464 @default.
- W2905058646 cites W2112612051 @default.
- W2905058646 cites W2114104545 @default.
- W2905058646 cites W2115235864 @default.
- W2905058646 cites W2118071133 @default.
- W2905058646 cites W2120076861 @default.
- W2905058646 cites W2120572492 @default.
- W2905058646 cites W2123106337 @default.
- W2905058646 cites W2126983941 @default.
- W2905058646 cites W2128542677 @default.
- W2905058646 cites W2129129812 @default.
- W2905058646 cites W2129265683 @default.
- W2905058646 cites W2130410032 @default.
- W2905058646 cites W2132546867 @default.
- W2905058646 cites W2138207763 @default.
- W2905058646 cites W2140729960 @default.
- W2905058646 cites W2141674733 @default.
- W2905058646 cites W2144912051 @default.
- W2905058646 cites W2158179945 @default.
- W2905058646 cites W2158789637 @default.
- W2905058646 cites W2159220884 @default.
- W2905058646 cites W2160811827 @default.
- W2905058646 cites W2162520885 @default.
- W2905058646 cites W2170846478 @default.
- W2905058646 cites W2183670742 @default.
- W2905058646 cites W2195725578 @default.
- W2905058646 cites W2205700110 @default.
- W2905058646 cites W2217028767 @default.
- W2905058646 cites W2226721679 @default.
- W2905058646 cites W2252568502 @default.
- W2905058646 cites W2299219969 @default.
- W2905058646 cites W2318605753 @default.
- W2905058646 cites W2502676454 @default.
- W2905058646 cites W2593741942 @default.
- W2905058646 cites W2702680930 @default.