Background Information on Palifermin
Palifermin is a recombinant human keratinocyte growth factor (KGF) that promotes the growth of epithelial cells. It was first discovered and produced by the biopharmaceutical corporation, Amgen. From the genetic perspective, the gene responsible for producing Palifermin, known as FGF7 or fibroblast growth factor 7, is located on chromosome 15q21.2. The protein structure of Palifermin is characterized by 163 amino acids and it possesses a molecular weight of approximately 19kDa.
Palifermin Function
The primary function of Palifermin is to stimulate the proliferation, differentiation, and migration of epithelial cells. It exerts its critical role in repairing damaged tissues and regenerating epithelia, including skin, digestive tract, and bronchial tubes. It acts by binding to KGF receptors (KGFR), which are primarily present in the epithelial cells of several organs. Moreover, Palifermin also reduces inflammation and tissue damage by modulating immune response.
Palifermin-Related Signaling Pathways
The function of Palifermin is mediated through specific signaling pathways. These include the PI3K/Akt pathway and the MAPK/ERK pathway.
PI3K/Akt Pathway: By binding to its receptor, Palifermin activates the PI3K/Akt pathway, which in turn triggers a series of downstream events, promoting cell survival, growth, and proliferation.
MAPK/ERK Pathway: Palifermin also activates the MAPK/ERK pathway, stimulating cell differentiation and proliferation.
Role of Palifermin in Diseases
Palifermin's role in disease manifestations is often related to its key function in epithelial cell repair and regeneration. Its deficiency or malfunctioning is associated with disorders involving epithelial damage and inflammation.
One of the most significant applications of Palifermin is in reducing the incidence and duration of severe oral mucositis in patients undergoing high-dose therapies for hematological malignancies. Furthermore, its role in chronic ulcerative stomatitis, a debilitating disease characterized by persistent mouth ulcers, is also under investigation.
Application of Palifermin in Medicine
In 2004, approved Palifermin (trade name Kepivance) for the treatment of severe oral mucositis in patients with hematological malignancies receiving myeloablative therapy. Palifermin, therefore, represents a promising therapeutic tool to improve the quality of life for patients receiving high-dose chemotherapy and radiation therapy.
List of Drug Candidates Related to Palifermin
The recombinant KGF, Palifermin, is presently the only drug of its class approved for oral mucositis. However, several other experimental drugs modulating the FGF7/KGFR pathway, such as Reparixin and Refanala, are under research for their potential therapeutic implications.
