[FGFR2 Fusion Gene-Positive Solid Tumors]

Fibroblast growth factor receptors (FGFR) are tyrosine kinases that regulate cellular responses including proliferation, survival, and migration. FGFR fusion genes arose from chromosomal translocations or deletions, lead to ligand-independent constitutive signal activation and contribute to carcinogenesis and cancer progression. FGFR2 fusion genes are identified in 7.4-13.6% of intrahepatic cholangiocarcinoma and 3.6% of perihilar cholangiocarcinoma. They are also reported in colorectal, prostate, and breast cancers, though at lower frequencies. Diagnosis methods are RT-PCR, RNA sequencing, FISH, and NGS. Comprehensive genomic profiling (CGP) tests are available clinically. Three FGFR inhibitors are currently approved. Pemigatinib (approved in 2021) demonstrated a response rate of 35.5%, futibatinib (approved in 2023) showed a response rate of 42%, and tasurgratinib (approved in 2024) achieved a response rate of 30.2%. The most common adverse event is hyperphosphatemia. Alopecia, diarrhea, nail disorders, and retinal detachment are also required attention. Polyclonal on-target resistance to pan-FGFR inhibitors and increasing of FGFR2 kinase domain resistance mutations based on treatment history has been reported. Novel therapeutics, such as highly selective FGFR2 inhibitors and next-generation inhibitors, are developed and are expected to improve prognosis for patients with FGFR2 fusion-positive solid tumors.