Potential dual role of KGF/KGFR as a target option in novel therapeutic strategies for the treatment of cancers and mucosal damages

Expert Opin Ther Targets. 2012 Apr;16(4):377-93. doi: 10.1517/14728222.2012.671813. Epub 2012 Mar 25.

Abstract

Introduction: Keratinocyte growth factor (KGF) and its receptor KGFR play a pivotal role in regulating cell proliferation, migration, differentiation and survival, in response to injury and tissue repair. Altered expression of this pathway in cancer opened the way to the development of targeted therapy to achieve KGFR inhibition. Nevertheless, KGF administration has been demonstrated to ameliorate oral mucositis resulting from chemoradiotherapy, besides protecting epithelial cells against radiation-induced damage.

Areas covered: This review focuses on the potential therapeutic interest of KGF/KGFR in two different areas: selective inhibition of KGFR signaling for the treatment of cancers characterized by upregulation of this pathway and administration of KGF to protect epithelial cells from induced damage. The review presents an overview of therapeutic strategies in both directions.

Expert opinion: KGF/KGFR signaling can contribute to enhancing the malignant potential of epithelial cells and to promoting tumorigenesis. On the other hand, the therapeutic use of KGF in cancer patients provides epithelial protection, reducing chemotherapy side effects. FGFRs have become attractive antitumor targets and various inhibitors have been used to contrast tumor cell growth. The identification of KGFR-specific molecules might represent a promising therapeutic strategy that could increase the window of available agents and treatment methods.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Fibroblast Growth Factor 7 / metabolism
  • Fibroblast Growth Factor 7 / therapeutic use*
  • Humans
  • Mucositis / drug therapy*
  • Mucositis / metabolism
  • Mucous Membrane / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Receptor, Fibroblast Growth Factor, Type 2 / antagonists & inhibitors*
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism

Substances

  • Fibroblast Growth Factor 7
  • Receptor, Fibroblast Growth Factor, Type 2
  • keratinocyte growth factor receptor