Time for arginine methylation: PRMT5 inhibition to advance cholangiocarcinoma treatment

Cholangiocarcinoma (CCA) is a highly aggressive adenocarcinoma of the biliary tract system with unsatisfactory therapeutic options. 1 Standard frontline treat-ment for unresectable or metastatic CCA consisting of cisplatin and gemcitabine combined with checkpoint inhibitors targeting programmed cell death ligand 1 or programmed cell death 1 offers objec-tive response rates of less than 30% and a median survival of approximately a year. 1 Targeted therapies against FGFR2 fusions and IDH1 mutations have gained regulatory approval in CCA, but these are applicable only in a minority of patients. 1 Disease-agnostic approvals of therapies targeting HER2 overexpression, NTRK fusions, RET fusions and microsatellite-unstable tumours also benefit patients with CCA, but again, only a small minority. Therefore, novel strategies to treat CCA are urgently needed.