FGF-7 (KGF)

Mechanism of Action

• Binds FGFR2IIIb with high specificity (does not activate FGFR1, FGFR2IIIc, FGFR3, FGFR4), restricting mitogenic effects to epithelial compartment
• Drives keratinocyte, intestinal epithelial, urothelial, and alveolar type II cell proliferation and migration
• Protects intestinal and oral epithelium from chemotherapy/radiation-induced DNA damage by upregulating repair enzymes and anti-apoptotic proteins
• Stimulates mucus secretion from goblet cells and promotes goblet cell differentiation
• Promotes alveolar type II pneumocyte proliferation and surfactant synthesis in lung injury models

Research Findings

• Palifermin (recombinant KGF) Phase III trial: 3 consecutive days of KGF before and after high-dose chemo/total body irradiation reduced severe oral mucositis incidence from 98% to 63% in hematologic cancer patients
• KGF reduced gastrointestinal toxicity and improved survival in mouse models of total body irradiation
• KGF promotes hair follicle growth and accelerates wound re-epithelialization in partial-thickness skin defect models
• KGF explored for radiation-induced lung injury (pneumonitis): alveolar type II cell protection in rodent models
• KGF mRNA expression in stroma markedly reduced in chronic non-healing wounds, contributing to impaired re-epithelialization

Research Protocols

• Palifermin (Kepivance) FDA-approved: 60 mcg/kg/day IV for 3 days before and 3 days after myeloablative chemotherapy
• Wound healing research: 10-100 ng/mL KGF on keratinocyte scratch assays; migration quantification
• Intestinal radiation protection: 5 mg/kg SC in mice 24 hours before lethal total-body irradiation; survival as endpoint
• Lung injury: 2-5 mg/kg intratracheal instillation before bleomycin challenge; measure alveolar damage by BAL

Interactions

• Heparin: required for FGFR2IIIb complex formation; heparin-binding domain mutations reduce KGF activity
• EGF and HGF: can synergize with KGF in epithelial migration and proliferation
• FGFR2IIIb: sole receptor; mutations in this splice isoform (Crouzon syndrome) affect KGF signaling in cranial sutures

Safety Profile

Palifermin FDA-approved 2004. Common adverse effects: mouth/tongue thickening, taste changes, skin rash, arthralgias (short-lived). Palifermin contraindicated in non-hematologic malignancies (FGFR2IIIb on epithelial tumors may promote tumor growth).

Legal & Regulatory

Palifermin (Kepivance): FDA-approved 2004 for oral mucositis in hematologic malignancies