FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4316804884> ?p ?o ?g. }

• W4316804884 abstract "Prostate cancer harboring BRCA1/2 mutations are often exceptionally sensitive to PARP inhibitors. However, genomic alterations in other DNA damage response genes have not been consistently predictive of clinical response to PARP inhibition. Here, we perform genome-wide CRISPR-Cas9 knockout screens in BRCA1/2-proficient prostate cancer cells and identify previously unknown genes whose loss has a profound impact on PARP inhibitor response. Specifically, MMS22L deletion, frequently observed (up to 14%) in prostate cancer, renders cells hypersensitive to PARP inhibitors by disrupting RAD51 loading required for homologous recombination repair, although this response is TP53-dependent. Unexpectedly, loss of CHEK2 confers resistance rather than sensitivity to PARP inhibition through increased expression of BRCA2, a target of CHEK2-TP53-E2F7-mediated transcriptional repression. Combined PARP and ATR inhibition overcomes PARP inhibitor resistance caused by CHEK2 loss. Our findings may inform the use of PARP inhibitors beyond BRCA1/2-deficient tumors and support reevaluation of current biomarkers for PARP inhibition in prostate cancer." @default.
• W4316804884 created "2023-01-17" @default.
• W4316804884 creator A5007413510 @default.
• W4316804884 creator A5010445228 @default.
• W4316804884 creator A5021830443 @default.
• W4316804884 creator A5025970058 @default.
• W4316804884 creator A5026961383 @default.
• W4316804884 creator A5030580122 @default.
• W4316804884 creator A5030895805 @default.
• W4316804884 creator A5032927153 @default.
• W4316804884 creator A5034110828 @default.
• W4316804884 creator A5046265881 @default.
• W4316804884 creator A5049979248 @default.
• W4316804884 creator A5066708432 @default.
• W4316804884 creator A5068445312 @default.
• W4316804884 creator A5070718477 @default.
• W4316804884 creator A5071445058 @default.
• W4316804884 creator A5071941735 @default.
• W4316804884 creator A5072104844 @default.
• W4316804884 creator A5072987336 @default.
• W4316804884 creator A5073123534 @default.
• W4316804884 creator A5073827712 @default.
• W4316804884 creator A5073984828 @default.
• W4316804884 date "2023-01-17" @default.
• W4316804884 modified "2023-10-06" @default.
• W4316804884 title "CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer" @default.
• W4316804884 cites W1578291413 @default.
• W4316804884 cites W1684904284 @default.
• W4316804884 cites W1879165674 @default.
• W4316804884 cites W1973268287 @default.
• W4316804884 cites W1984143603 @default.
• W4316804884 cites W2008529786 @default.
• W4316804884 cites W2009007206 @default.
• W4316804884 cites W2015360671 @default.
• W4316804884 cites W2021851245 @default.
• W4316804884 cites W2028044172 @default.
• W4316804884 cites W2034317592 @default.
• W4316804884 cites W2046260231 @default.
• W4316804884 cites W2049219444 @default.
• W4316804884 cites W2058957446 @default.
• W4316804884 cites W2078455244 @default.
• W4316804884 cites W2092835558 @default.
• W4316804884 cites W2096957390 @default.
• W4316804884 cites W2098276373 @default.
• W4316804884 cites W2098737737 @default.
• W4316804884 cites W2100122648 @default.
• W4316804884 cites W2100253170 @default.
• W4316804884 cites W2102198419 @default.
• W4316804884 cites W2118118849 @default.
• W4316804884 cites W2123696077 @default.
• W4316804884 cites W2124664018 @default.
• W4316804884 cites W2125824383 @default.
• W4316804884 cites W2130410032 @default.
• W4316804884 cites W2130447102 @default.
• W4316804884 cites W2134526812 @default.
• W4316804884 cites W2135785842 @default.
• W4316804884 cites W2145137051 @default.
• W4316804884 cites W2148964728 @default.
• W4316804884 cites W2153926167 @default.
• W4316804884 cites W2157458089 @default.
• W4316804884 cites W2166374178 @default.
• W4316804884 cites W2169228223 @default.
• W4316804884 cites W2169456326 @default.
• W4316804884 cites W2179438025 @default.
• W4316804884 cites W2201689894 @default.
• W4316804884 cites W2259938310 @default.
• W4316804884 cites W2295085830 @default.
• W4316804884 cites W2318981985 @default.
• W4316804884 cites W2343436177 @default.
• W4316804884 cites W2346683950 @default.
• W4316804884 cites W2410908789 @default.
• W4316804884 cites W2431032595 @default.
• W4316804884 cites W2473363865 @default.
• W4316804884 cites W2473878031 @default.
• W4316804884 cites W2542071790 @default.
• W4316804884 cites W2567986926 @default.
• W4316804884 cites W2571250257 @default.
• W4316804884 cites W2587831721 @default.
• W4316804884 cites W2588135595 @default.
• W4316804884 cites W2594301310 @default.
• W4316804884 cites W2596164112 @default.
• W4316804884 cites W2605336808 @default.
• W4316804884 cites W2623263876 @default.
• W4316804884 cites W2747878742 @default.
• W4316804884 cites W2755290882 @default.
• W4316804884 cites W2769765627 @default.
• W4316804884 cites W2786726389 @default.
• W4316804884 cites W2787958170 @default.
• W4316804884 cites W2789900707 @default.
• W4316804884 cites W2791912178 @default.
• W4316804884 cites W2796153844 @default.
• W4316804884 cites W2798183676 @default.
• W4316804884 cites W2808113406 @default.
• W4316804884 cites W2809570092 @default.
• W4316804884 cites W2810583998 @default.
• W4316804884 cites W2811060920 @default.
• W4316804884 cites W2883664363 @default.
• W4316804884 cites W2886286091 @default.
• W4316804884 cites W2889330650 @default.
• W4316804884 cites W2900310474 @default.

• next