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| Mechanism of Action |
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Keratinocyte growth factor (KGF) is an endogenous protein in the fibroblast growth factor (FGF) family that binds to the KGF receptor.
Binding of KGF to its receptor has been reported to result in proliferation, differentiation, and migration of epithelial cells.
The KGF receptor, one of four receptors in the FGF family, has been reported to be present on epithelial cells in many
tissues examined including the tongue, buccal mucosa, esophagus, stomach, intestine, salivary gland, lung, liver, pancreas, kidney,
bladder, mammary gland, skin (hair follicles and sebaceous gland), and the lens of the eye.
The KGF receptor has been reported to not be present on cells of the hematopoietic lineage. Endogenous KGF is produced by mesenchymal
cells and is upregulated in response to epithelial tissue injury.1
Kepivance® (palifermin) is a recombinant form of human keratinocyte
growth factor (KGF). Kepivance® has been shown to enhance
the growth of human epithelial tumor cell lines in vitro at concentrations ≥10
mcg/mL (> 15-fold higher than average therapeutic
concentrations in humans). Kepivance® binds to the KGF
receptor on the cell surface, acting as both a growth and survival factor
by stimulating epithelial cell proliferation, differentiation, and migration
in addition to upregulating cytoprotective mechanisms.1-7
Figure 1. The 5 Phases of
Oral Mucositis and the Potential Mechanisms of Kepivance® *†2,7-13
| * |
Adapted from Sonis, Nat Rev Cancer. 2004;4:277-284. |
| † |
Proposed mechanism of action. |
| ‡ |
Reactive oxygen species. |
| 1 |
Kepivance® (palifermin) prescribing information. |
| 2 |
Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for
hematologic cancers. N Engl J Med. 2004;351:2590-2598. |
| 3 |
Rubenstein EB, Peterson DE, Schubert M, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer. 2004;100(suppl 9):2026-2046. |
| 4 |
Danilenko DM. Preclinical and early clinical development of keratinocyte growth factor, an epithelial-specific tissue growth factor. Toxicol Pathol. 1999;27:64-71. |
| 5 |
Werner S. Keratinocyte growth factor: a unique player in epithelial repair processes. Cytokine & Growth Factor Reviews. 1998;9:153-165. |
| 6 |
Farrell CL, Rex KL, Chen JN, et al. The effects of keratinocyte growth factor in preclinical models of mucositis. Cell Prolif. 2002;35(suppl 1):78-85. |
| 7 |
Jonas CR, Farrell CL, Scully S, et al. Enteral nutrition and keratinocyte growth factor regulate expression of glutathione-related enzyme messenger RNAs in rat intestine. JPEN J Parenter Enteral Nutr. 2000;24:67-75. |
| 8 |
Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4:277-284. |
| 9 |
Takeoka M, Ward WF, Pollack H, Kamp DW, Panos RJ. KGF facilitates repair of radiation-induced DNA damage in alveolar epithelial cells. Am J Physiol. 1997;272:L1174-L1180. |
| 10 |
Wu KI, Pollack N, Panos RJ, et al. Keratinocyte
growth factor promotes alveolar epithelial cell DNA repair after H2O2
exposure. Am J Physiol. 1998;275:L780-L787. |
| 11 |
Panoskaltsis-Mortari A, Taylor PA, Rubin JS, et al. Keratinocyte growth factor facilitates alloengraftment and ameliorates graft-versus-host disease in mice by a mechanism independent of repair of conditioning-induced tissue injury. Blood. 2000;96:4350-4356. |
| 12 |
Potten CS, Booth D, Cragg NJ, O'Shea JA, Tudor GL, Booth C. Cell kinetic studies in the murine ventral tongue epithelium: the effects of repeated exposure to keratinocyte growth factor. Cell Prolif. 2002;35(suppl 1):22-31. |
| 13 |
Farrell CL, Rex KL, Kaufman SA, et al. Effects of keratinocyte growth factor in the squamous epithelium of the upper aerodigestive tract of normal and irradiated mice. Int J Radiat Biol. 1999;75:609-620. |
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ABOUT ORAL MUCOSITIS
ABOUT KEPIVANCE®
TOOLS AND RESOURCES
FOR NURSES
FOR PHARMACISTS
IMPORTANT PRODUCT SAFETY INFORMATION
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