CPI-169

Collectively, our study highlighted the potential of the therapeutic combination of FGFR4 and EZH2 inhibitors, which would provide new references for the further development of clinical treatment strategies for HCC.

Given the known interplay between EZH2 and MYC downstream signaling in malignant B cells, we undertook the simultaneous evaluation of two epigenetic drugs that interfere with EZH2 methyltransferase activity and BRD4-mediated control of MYC transcription, namely CPI169 and CPI203; using preclinical models of DLBCL and FL with distinct EZH2 mutational status. Gene expression profile analysis, followed by automated exploratory data analysis and validation by a siRNA screening, further identified the PI3K/AKT-regulated gene and mitosis regulator, YPEL2; as a crucial factor involved in the efficacy of MYC/EZH2 dual targeting in vitro and in vivo . Conclusion These results provide a first preclinical evidence that simultaneous targeting of MYC and EZH2 is a safe and efficient approach that can be monitored by specific biomarkers in aggressive lymphoid tumors of germinal center origin.