Tyrosine Kinase Inhibition in Mastocytosis: KIT and Beyond KIT

Immunol Allergy Clin North Am. 2018 Aug;38(3):527-543. doi: 10.1016/j.iac.2018.04.007.

Abstract

Mastocytosis is a group of rare disorders characterized by abnormal accumulation of mast cells in one or several organs. Mastocytosis can be seen at any age; but, in adults, the disease is usually systemic and chronic. Patients with indolent systemic mastocytosis (SM) are usually treated symptomatically, but cytoreductive treatments are needed in more advanced SM. In most patients with SM, an activating KIT D816V mutation is found. Thus, patients with advanced SM benefit from treatment with KIT-targeting tyrosine kinase inhibitors. However, none of these drugs are curative; new targeted drugs or combinations are still needed to improve patients' outcome.

Keywords: Advanced disease; Drug development; KIT mutations; Mast cells; Mastocytosis; Targeted drugs; Tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Cytoreduction Surgical Procedures
  • Humans
  • Mast Cells / physiology*
  • Mastocytosis / drug therapy*
  • Mastocytosis / metabolism
  • Molecular Targeted Therapy
  • Mutation / genetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism*

Substances

  • Protein Kinase Inhibitors
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit