EPZ-6438 is an inhibitor of the histone methyltransferase EZH2 that has recently entered clinical trials for MPM patients due to its antiproliferative effects on tumor cells [21,22]; however, the impact of this epigenetic modulator on the TME and the effects of TME on MPM cell responsiveness to EZH2 inhibitors are still largely unexplored. This evidence concerns the gene EZH2 and neoplasm.