Fig. 1: Extracellular FGFR2 alterations, downstream FGFR2 activation in the tumor of Patient Case 1, and clinical course during treatment with pazopanib.

a Schematic overview of FGFR2 alterations of Case 1 and Case 2 using ChemDraw 19.1. The variant F276C (Case 1) is located within the Ig-like domain 3 of the extracellular receptor region (green circle). The c.1107_1113delinsCTCG alteration (Case 2) is located within the juxtamembrane domain of the receptor (red circle). b Structure of FGFR2 with the extracellular variant F276C of Case 1 using Schrödinger Suite 2020-1 and PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC. The ligand FGF1 (green ribbon) is bound to FGFR2 (orange ribbon). F276C mutation is shown in the magenta sphere. The mutated residue is located far away from the receptor–ligand interface. c Immunohistochemistry of FGFR2 downstream targets in tumor biopsy of Case 1 prior to the treatment with pazopanib. Scale bar 100 µm, magnification x200, objective x20. d Before treatment of Case 1 with pazopanib (baseline), a large tumor mass was seen centrally in the liver compressing the left bile duct with secondary upstream bile stasis in a CT scan. The mass showed a slightly heterogeneous enhancement with predominantly hyper-enhancement in the late arterial enhancement phase. 5 months after initiation of pazopanib treatment, the mass showed a significant (>20%) reduction in size and almost complete reduction in tumor enhancement (>80%) and the biliary stasis had vanished. These findings stayed unchanged also 9 months after treatment onset. Progression according to RECIST 1.1 was seen 11 months after treatment initiation.