Targeting FGFR inhibition in cholangiocarcinoma

Cholangiocarcinomas (CCAs) are rare but aggressive tumours of the bile ducts, which often diagnosed at an advanced stage and have poor outcomes on systemic therapy. Somatic alterations with therapeutic implications been identified in almost half CCAs, particular intrahepatic CCA (iCCA), subtype arising from ducts within liver. Among patients CCA, fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements occur exclusively iCCA, where they estimated to be found up 10–15% patients. Clinical trials for selective FGFR kinase inhibitors shown consistent activity these agents previously treated iCCA harbouring alterations. Current show differences their structure, mechanisms target engagement, specificities FGFR1, 2, 3 4 other related kinases. These offer potential improve FGFR-driven impact variations molecular profiles efficacy, safety, acquired resistance mechanisms, patients’ health-related quality life remains fully characterized. The most common adverse event associated is hyperphosphatemia, on-target off-tumour effect FGFR1 inhibition, strategies manage this include dose adjustment, chelators, use a low phosphate diet. As targeted enter clinic testing actionable mutations monitoring emergence will essential.