FGFRtargeted

FGFRtargeted refers to therapeutic strategies that inhibit the fibroblast growth factor receptor (FGFR) signaling axis in cancer and other diseases. The FGFR family comprises four receptor tyrosine kinases (FGFR1-4) that drive cell proliferation, survival, and angiogenesis when aberrantly activated by mutations, fusions, amplifications, or ligand overexpression. FGFR-targeted therapies include small-molecule tyrosine kinase inhibitors (TKIs) that block ATP binding in the FGFR kinase domain, as well as selective inhibitors versus pan-FGFR activity, and, more recently, antibody-based approaches and ligand traps in development.

In oncology, FGFR alterations occur across several tumors, most prominently FGFR2 fusions in cholangiocarcinoma and FGFR3 alterations in urothelial carcinoma and bladder cancer. FGFR-targeted drugs have achieved regulatory approvals in selected indications, notably FGFR inhibitors such as erdafitinib for metastatic urothelial carcinoma with FGFR alterations, and pemigatinib for cholangiocarcinoma harboring FGFR2 fusions. Other inhibitors and candidates are under evaluation in gastric cancer, glioma, hepatobiliary cancers, and lung cancer, among others.

Patient selection relies on molecular profiling to identify actionable FGFR alterations using next-generation sequencing or targeted assays. Resistance to FGFR-targeted therapy commonly emerges through secondary mutations in the FGFR kinase domain or activation of alternative signaling pathways, prompting development of next-generation inhibitors and combination strategies.

Common adverse effects reflect FGFR inhibition, including hyperphosphatemia, stomatitis, dermatologic and nail changes, fatigue, and ophthalmic toxicity. Ongoing research aims to expand indications, overcome resistance, and optimize sequencing with other systemic therapies.