Facchinetti et al.,30 in patients with bladder cancer treated with FGFR inhibitors, described the occurrence of FGFR mutations in the tyrosine kinase domain as well as co-existing alterations in the PI3K-mTOR -including TSC1 and TSC2 mutations- and EGFR pathways, all likely responsible for primary or acquired resistance to FGFR inhibitors. Here, TSC2 is linked to urinary bladder cancer.