Keratinocyte growth factor expression and activity in cancer: implications for use in patients with solid tumors.
Keratinocyte growth factor (KGF) is a locally acting epithelial mitogen that is produced by cells of mesenchymal origin and has an important role in protecting and repairing epithelial tissues. Use of recombinant human KGF (palifermin) in patients with hematologic malignancies reduces the incidence and duration of severe oral mucositis experienced after intensive chemoradiotherapy. These results suggest that KGF may be useful in the treatment of patients with other kinds of tumors, including those of epithelial origin. However, its application in this context raises issues that were not pertinent to its use in hematologic cancer because epithelial tumor cells, unlike blood cells, often express the KGF receptor (FGFR2b). Thus, it is important to examine whether KGF could promote the growth of epithelial tumors or protect such tumor cells from the effects of chemotherapy agents. Analyses of KGF and FGFR2b expression in tumor specimens and of KGF activity on transformed cells in vitro and in vivo do not indicate a definitive role for KGF in tumorigenesis. On the contrary, restoring FGFR2b expression to certain malignant cells can induce cell differentiation or apoptosis. However, other observations suggest that, in specific situations, KGF may contribute to epithelial tumorigenesis. Thus, further studies are warranted to examine the nature and extent of KGF involvement in these settings. In addition, clinical trials in patients with solid tumors are underway to assess the potential benefits of using KGF to protect normal tissue from the adverse effects of chemoradiotherapy and its possible impact on clinical outcome.
Finch
Paul W
PW
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Building 37, Room 2042, 37 Convent Drive, MSC 4256, Bethesda, MD 20892-4256, USA.
Rubin
Jeffrey S
JS
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D051523:Fibroblast Growth Factor 7 / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D015398:Signal Transduction
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D051497:Receptor, Fibroblast Growth Factor, Type 2