title: Oncolytic potential of a novel KGFR tyrosine kinase inhibitor using a KGFR-selective breast cancer xenograft model.
abstract: BACKGROUND
  Keratinocyte growth factor (KGF)/KGF receptor (KGFR) signaling produces a rapid increase in the progression of breast cancer. Molecular modeling was used to create a group of KGFR-selective kinase inhibitors (TKI). Compound L-27 is a potent and selective KGFR TKI. The present study examined the oncolytic potential of L-27 using a breast cancer xenograft model.
  
  
  METHODS
  An orthotopic xenograft model was developed with KGF-transfected MCF-7 cells to examine the influence of L-27 upon KGFR-mediated tumor progression.
  
  
  RESULTS
  L-27 was found to produce a dose-related reduction in the growth and metastasis of mouse xenograft tumors. Furthermore, L-27 treatment did not produce any signs of gross toxicity.
  
  
  CONCLUSIONS
  L-27 was found to reduce the growth and metastasis of MCF-7 tumor xenografts with elevated expression of KGF. Thus, KGFR TKI may provide a new therapeutic approach for the treatment of breast and other types of cancer.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, U.S.A.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Kesinger
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, U.S.A.
authors.forename: Meghna
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Department of Surgery, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, U.S.A.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Lerner
authors.affiliation: Department of Surgery, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, U.S.A.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brackett
authors.affiliation: VA Medical Center, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, U.S.A.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Brueggemeier
authors.affiliation: VA Medical Center, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, U.S.A.
authors.forename: Pui-Kui
authors.initials: PK
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, U.S.A. tom-pento@ouhsc.edu.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Pento
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor
keywords: GFP xenograft assay; breast cancer; metastasis