DNER and neoplasm: In contrast to direct small-molecule inhibitors of driver oncoproteins where specific DNA mutations serve as reliable biomarkers, the establishment of predictive markers of BET inhibition is heavily affected by the underlying heterogeneous genetic and epigenetic landscape of human cancers, including lung cancers, that can lead to the activation of different driver genes in specific individual cancers, or even in different subclones of the same tumor [51].