Figure 6.

In vitro and in vivo evaluation of the activity of selective FGFR inhibitors against FGFR2 kinase domain mutations. A, IC₅₀ values of seven reversible FGFR inhibitors (and their average) against parental Ba/F3, FGFR2::BICC1 Ba/F3 (wild-type, WT), and 17 mutants. B, Graphical representation of the IC₅₀ values of the two irreversible FGFR inhibitors futibatinib and lirafugratinib (and their average) against parental Ba/F3, FGFR2::BICC1 Ba/F3 (WT), and 17 mutants. We created two different cut-off thresholds, given the lower potency of zoligratinib, derazantinib, and rogaratinib against WT FGFR2::BICC1 Ba/F3. In A and B, IC₅₀ values (nmol/L) are reported as means of ≥3 independent datasets. C, Tumor growth kinetics in PDX models established from patients with cholangiocarcinoma, exposed to four FGFR inhibitors. # MR332 PDX was established from the liver tissue biopsy harboring FGFR2 V565F, whereas the bone lesion harbored FGFR2 V565L (see Fig. 2C). q.d.: quaque die (i.e., daily).