Mengnuo Chen, Sara Mainardi, Cor Lieftink, Arno Velds, Iris de Rink, Chen Yang, Hendrik J Kuiken, Ben Morris, Finn Edwards, Fleur Jochems, Olaf van Tellingen, Manon Boeije, Natalie Proost, Robin A Jansen, Shifan Qin, Haojie Jin, J C Koen van der Mijn, Arnout Schepers, Subramanian Venkatesan, Wenxin Qin, Roderick L Beijersbergen, Liqin Wang, René Bernards
Drug-tolerant persisters (DTPs) are a rare subpopulation of cells within a tumor that can survive therapy through nongenetic adaptive mechanisms to develop relapse and repopulate the tumor following drug withdrawal. Using a cancer cell line with an engineered suicide switch to kill proliferating cells, we perform both genetic screens and compound screens to identify the inhibition of bromodomain and extraterminal domain (BET) proteins as a selective vulnerability of DTPs. BET inhibitors are especially detrimental to DTPs that have reentered the cell cycle (DTEPs) in a broad spectrum of cancer types...
March 19, 2024: Cell reports medicine