NF1 and cancer: Additionally, PRC2 loss induces an epigenetic switch in NF1 mutant cancers, sensitizing these cancers to BRD4-based therapies.714 Collectively, different strategies are developed to target cancers with EZH2 hyperactivity (inhibition of EZH2 enzymatic activity alone, EZH1/2 dual inhibition, or suppression of both canonical and non-canonical activity of EZH2) or with PRC2 loss (synthetic lethality with other targeted therapy), which provides an excellent paradigm to target a histone modifier with context-dependent functions and multiple acting mechanisms.