John Wrangle, Wei Wang, Alexander Koch, Hariharan Easwaran, Helai P Mohammad, Frank Vendetti, Wim Vancriekinge, Timothy Demeyer, Zhengzong Du, Princy Parsana, Kristen Rodgers, Ray-Whay Yen, Cynthia A Zahnow, Janis M Taube, Julie R Brahmer, Scott S Tykodi, Keith Easton, Richard D Carvajal, Peter A Jones, Peter W Laird, Daniel J Weisenberger, Salina Tsai, Rosalyn A Juergens, Suzanne L Topalian, Charles M Rudin, Malcolm V Brock, Drew Pardoll, Stephen B Baylin
Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples...
November 2013: Oncotarget