Strategies that aim to take advantage of synthetic lethality in MPM are promising as MiST2 showed clinical activity with CDK4/6 inhibition in CDKN2A-deleted mesothelioma, and clinical trials are ongoing to assess the effectiveness of YAP/TEAD and PRMT5 inhibitors in NF2- and MTAP-mutated MPM, respectively. Here, PRMT5 is linked to mesothelioma.