FGFR2 fusion transcripts generated by chromosomal rearrangements are found in about 10–15% of patients with iCCA.37 The efficacy of first-generation tyrosine kinase inhibitors (F-TKIs) in iCCA patients is limited by the emergence of secondary resistance, a major genetic determinant of which is represented by on-target mutations that prevent access of F-TKIs to the FGFR2 ATP-binding pocket.38 Resistance mutations in FFPs are most often polyclonal. This evidence concerns the gene FGFR2 and infantile convulsions and choreoathetosis.