Shaokun Shu, Hua-Jun Wu, Jennifer Y Ge, Rhamy Zeid, Isaac S Harris, Bojana Jovanović, Katherine Murphy, Binbin Wang, Xintao Qiu, Jennifer E Endress, Jaime Reyes, Klothilda Lim, Alba Font-Tello, Sudeepa Syamala, Tengfei Xiao, Chandra Sekhar Reddy Chilamakuri, Evangelia K Papachristou, Clive D'Santos, Jayati Anand, Kunihiko Hinohara, Wei Li, Thomas O McDonald, Adrienne Luoma, Rebecca J Modiste, Quang-De Nguyen, Brittany Michel, Paloma Cejas, Cigall Kadoch, Jacob D Jaffe, Kai W Wucherpfennig, Jun Qi, X Shirley Liu, Henry Long, Myles Brown, Jason S Carroll, Joan S Brugge, James Bradner, Franziska Michor, Kornelia Polyak
BET bromodomain inhibitors (BBDIs) are candidate therapeutic agents for triple-negative breast cancer (TNBC) and other cancer types, but inherent and acquired resistance to BBDIs limits their potential clinical use. Using CRISPR and small-molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance, we identified synthetic lethal interactions with BBDIs and genes that, when deleted, confer resistance. We observed synergy with regulators of cell cycle progression, YAP, AXL, and SRC signaling, and chemotherapeutic agents...
June 18, 2020: Molecular Cell