Therapeutic modulation of KIT ligand in melanocytic disorders with implications for mast cell diseases

Exp Dermatol. 2024 May;33(5):e15091. doi: 10.1111/exd.15091.

Abstract

KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders. KIT ligand regulation is complex but efficient targeting of this system would be of significant benefit to those suffering from melanocytic or mast cell disorders. Herein, we review the known associations of this pathway with cutaneous diseases and the regulators of this system both in skin and in the more well-studied germ cell system. Exogenous agents modulating this pathway will also be presented. Ultimately, we will review potential therapeutic opportunities to help our patients with melanocytic and mast cell disease processes potentially including vitiligo, hair greying, melasma, urticaria, mastocytosis and melanoma.

Keywords: KIT; KIT ligand; mast cells; melanocytes; pigmentation.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Mast Cells* / metabolism
  • Mastocytosis* / drug therapy
  • Mastocytosis* / metabolism
  • Melanocytes* / metabolism
  • Melanoma / drug therapy
  • Melanoma / metabolism
  • Pigmentation Disorders / drug therapy
  • Proto-Oncogene Proteins c-kit* / metabolism
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / metabolism
  • Stem Cell Factor* / metabolism
  • Vitiligo / drug therapy
  • Vitiligo / metabolism
  • Vitiligo / therapy

Substances

  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit
  • KIT protein, human