Tumor cells frequently rewire their metabolism to satisfy increased demands for cellular building blocks. The relative abundance of pyruvate kinase M1 (PKM1) versus PKM2 mediated by alternative splicing of the Pkm gene has been implicated in the shift between oxidative phosphorylation and aerobic glycolysis. A recent study by Xia et al. in Cancer Research examined the role of PKM2 in urothelial cancer. The investigators examined the effect of PKM2 silencing in oncogenic HRAS-driven urothelial cancer murine models. Silencing PKM2 in mouse urothelial cells did not affect tumor initiation but inhibited the growth and maintenance of HRAS-driven tumors. Pharmacologic inhibition of PKM2 recapitulated this phenotype.