I purified keratinocyte growth factor (KGF, also known as FGF7) as a postdoctoral fellow in the late 1980s, and have been involved in its research ever since. Milestones achieved in our lab included molecular cloning and recombinant expression of the growth factor, characterization of its predominant epithelial cell specificity, identification and cloning of its tyrosine kinase cell surface receptors, FGFR2IIIb isoforms that arise from alternative splicing primarily confined to epithelial cells. Several collaborative studies broadened our understanding of its biological activities, including the first report documenting its remarkable cytoprotective effects. Amgen, Inc. licensed patent rights to KGF for the development of therapeutic products. Preclinical research performed by Amgen scientists and associates provided further evidence that KGF had therapeutic potential in reducing damage to epithelia following exposure to chemo/radiotherapy. A series of clinical trials tested the safety and efficacy of KGF in decreasing the incidence and duration of severe oral mucositis in patients receiving intensive cancer therapy. This work culminated in a successful phase 3 trial involving patients with hematologic malignancies who received high dose chemo/radiotherapy prior to autologous peripheral blood progenitor cell transplantation. Based on these results, the FDA approved use of KGF in this clinical context and the product went on the market in January2005 (trademark name is Kepivance, generic name is palifermin). Additional clinical trials are underway to explore its utility in the solid tumor setting, and other clinical applications are under consideration.
