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10.1126/scitranslmed.aal1645 http://scihub22266oqcxt.onion/10.1126/scitranslmed.aal1645 C5705017!5705017!28747513     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Sci+Transl+Med 2017 ; 9 (400): ä Nephropedia Template TP {{tp|p=28747513|t=2017. Repression of BET activity sensitizes homologous recombination?proficient cancers to PARP inhibition |pdf=|usr=}}{{28747513}} gab.com Text Repression of BET activity sensitizes homologous recombination proficient cancers to PARP inhibition JO: Sci Transl Med http://www.kidney.de/pget.php?&tw=1&pmid=28747513 #FOAvip Strategies to enhance response to poly(adenosine diphosphate?ribose) polymerase inhibitor (PARPi) in primary and acquired homologous recombination (HR)?proficient tumors would be a major advance in cancer care. We used a drug synergy screen that combined a PARPi, olaparib, with 20 well-characterized epigenetic drugs and identified bromodomain and extraterminal domain inhibitors (BETis; JQ1, I-BET762, and OTX015) as drugs that acted synergistically with olaparib in HR-proficient cancer cells. Functional assays demonstrated that repressed BET activity reduces HR and thus enhances PARPi-induced DNA damage in cancer cells. We also found that inhibition or depletion of BET proteins impairs transcription of BRCA1 and RAD51, two genes essential for HR. Moreover, BETi treatment sensitized tumors to PARP inhibition in preclinical animal models of HR-proficient breast and ovarian cancers. Finally, we showed that the BRD4 gene was focally amplified across 20 types of common cancers. Combination with BETi could greatly expand the utility of PARP inhibition to patients with HR-proficient cancer. Twit Text FOAVip Repression of BET activity sensitizes homologous recombination proficient cancers to PARP inhibition ????Sci Transl Med http://www.kidney.de/pget.php?&tw=1&pmid=28747513 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28747513 #FOAvip English Wikipedia <ref>{{Cite pmid|28747513}}</ref> Repression of BET activity sensitizes homologous recombination?proficient cancers to PARP inhibition #MMPMID28747513 Yang L; Zhang Y; Shan W; Hu Z; Yuan J; Pi J; Wang Y; Fan L; Tang Z; Li C; Hu X; Tanyi JL; Fan Y; Huang Q; Montone K; Dang CV; Zhang L Sci Transl Med 2017[Jul]; 9 (400): ä PMID28747513show ga Strategies to enhance response to poly(adenosine diphosphate?ribose) polymerase inhibitor (PARPi) in primary and acquired homologous recombination (HR)?proficient tumors would be a major advance in cancer care. We used a drug synergy screen that combined a PARPi, olaparib, with 20 well-characterized epigenetic drugs and identified bromodomain and extraterminal domain inhibitors (BETis; JQ1, I-BET762, and OTX015) as drugs that acted synergistically with olaparib in HR-proficient cancer cells. Functional assays demonstrated that repressed BET activity reduces HR and thus enhances PARPi-induced DNA damage in cancer cells. We also found that inhibition or depletion of BET proteins impairs transcription of BRCA1 and RAD51, two genes essential for HR. Moreover, BETi treatment sensitized tumors to PARP inhibition in preclinical animal models of HR-proficient breast and ovarian cancers. Finally, we showed that the BRD4 gene was focally amplified across 20 types of common cancers. Combination with BETi could greatly expand the utility of PARP inhibition to patients with HR-proficient cancer. äRepression of BET activity sensitizes homologous recombination?profici(epmc).pdf DeepDyve Pubget Overpricing