DHODH and mesothelioma: Xu et al deliver three pioneering advances: First, they ascribe a pyrimidine‐enriched transcriptome specifically to NF2-altered mesothelioma; second, they demonstrate that YAP directly binds the CAD promoter and a DHODH enhancer, markedly increasing de novo pyrimidine biosynthesis pathway flux and creating a vulnerability to DHODH inhibitors; lastly, they demonstrate potent in vivo synergy of such compounds with cisplatin, lending hope for possible future integration of pyrimidine pathway blockade into current treatment regimens (Fig. 1).