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10.1038/nm.4407 http://scihub22266oqcxt.onion/10.1038/nm.4407 C5677540!5677540!28967920     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Med 2017 ; 23 (11): 1362-8 Nephropedia Template TP {{tp|p=28967920|t=2017. Keap1 loss promotes Kras-driven lung cancer and results in a dependence on glutaminolysis |pdf=|usr=}}{{28967920}} gab.com Text Keap1 loss promotes Kras-driven lung cancer and results in a dependence on glutaminolysis JO: Nat Med http://www.kidney.de/pget.php?&tw=1&pmid=28967920 #FOAvip Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein1. One approach to addressing this challenge is to define frequently co-occurring mutations with KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function (LOF) mutations in Kelch-like ECH-associated protein 1 (KEAP1)2-4, a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response5-10. The high frequency of mutations in KEAP1 suggests an important role for the oxidative stress response in lung tumorigenesis. Using a CRISPR/Cas9-based approach in a mouse model of Kras-driven LUAD we examined the effects of Keap1 loss in lung cancer progression. We show that loss of Keap1 hyper-activates Nrf2 and promotes Kras-driven LUAD. Combining CRISPR/Cas9-based genetic screening and metabolomic analyses, we show that Keap1/Nrf2-mutant cancers are dependent on increased glutaminolysis, and this property can be therapeutically exploited through the pharmacological inhibition of glutaminase. Finally, we provide a rationale for sub-stratification of human lung cancer patients with KRAS-KEAP1 or -NRF2-mutant tumors as likely to respond to glutaminase inhibition. Twit Text FOAVip Keap1 loss promotes Kras-driven lung cancer and results in a dependence on glutaminolysis ????Nat Med http://www.kidney.de/pget.php?&tw=1&pmid=28967920 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28967920 #FOAvip English Wikipedia <ref>{{Cite pmid|28967920}}</ref> Keap1 loss promotes Kras-driven lung cancer and results in a dependence on glutaminolysis #MMPMID28967920 Romero R; Sayin VI; Davidson SM; Bauer MR; Singh SX; LeBoeuf SE; Karakousi TR; Ellis DC; Bhutkar A; Sanchez-Rivera FJ; Subbaraj L; Martinez B; Bronson RT; Prigge JR; Schmidt EE; Thomas CJ; Goparaju C; Davies A; Dolgalev I; Heguy A; Allaj V; Poirier JT; Moreira AL; Rudin CM; Pass HI; Vander Heiden MG; Jacks T; Papagiannakopoulos T Nat Med 2017[Nov]; 23 (11): 1362-8 PMID28967920show ga Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein1. One approach to addressing this challenge is to define frequently co-occurring mutations with KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function (LOF) mutations in Kelch-like ECH-associated protein 1 (KEAP1)2-4, a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response5-10. The high frequency of mutations in KEAP1 suggests an important role for the oxidative stress response in lung tumorigenesis. Using a CRISPR/Cas9-based approach in a mouse model of Kras-driven LUAD we examined the effects of Keap1 loss in lung cancer progression. We show that loss of Keap1 hyper-activates Nrf2 and promotes Kras-driven LUAD. Combining CRISPR/Cas9-based genetic screening and metabolomic analyses, we show that Keap1/Nrf2-mutant cancers are dependent on increased glutaminolysis, and this property can be therapeutically exploited through the pharmacological inhibition of glutaminase. Finally, we provide a rationale for sub-stratification of human lung cancer patients with KRAS-KEAP1 or -NRF2-mutant tumors as likely to respond to glutaminase inhibition. äKeap1 loss promotes Kras-driven lung cancer and results in a dependenc(epmc).pdf DeepDyve Pubget Overpricing