David H Peng, Samrat T Kundu, Jared J Fradette, Lixia Diao, Pan Tong, Lauren A Byers, Jing Wang, Jaime Rodriguez Canales, Pamela A Villalobos, Barbara Mino, Yanan Yang, Rosalba Minelli, Michael D Peoples, Christopher A Bristow, Timothy P Heffernan, Alessandro Carugo, Ignacio I Wistuba, Don L Gibbons
Mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors have failed to show clinical benefit in Kirsten rat sarcoma ( KRAS ) mutant lung cancer due to various resistance mechanisms. To identify differential therapeutic sensitivities between epithelial and mesenchymal lung tumors, we performed in vivo small hairpin RNA screens, proteomic profiling, and analysis of patient tumor datasets, which revealed an inverse correlation between mitogen-activated protein kinase (MAPK) signaling dependency and a zinc finger E-box binding homeobox 1 (ZEB1)-regulated epithelial-to-mesenchymal transition...
March 13, 2019: Science Translational Medicine