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Pharmacol Ther. 2019 May;197:11-37. doi: 10.1016/j.pharmthera.2018.12.008. Epub 2018 Dec 14.

KIT as a therapeutic target for non-oncological diseases.

Author information

1
Aix Marseille Université, INSERM, INRA, C2VN, Marseille, France.
2
Department of Respiratory Diseases-CHRU Montpellier, U1046 INSERM, UMR9214 CNRS University of Montpellier, Montpellier, France.
3
INSERM, CNRS, Institut Paoli Calmettes, CRCM, Centre de référence des mastocytoses, Equipe labellisée Ligue National contre le cancer, Aix-Marseille Université, Marseille, France.
4
Aix Marseille Université, INSERM, INRA, C2VN, Marseille, France; Clinique des Bronches, Allergies et Sommeil, Hôpital Nord, AP-HM, Marseille, France. Electronic address: pascal.chanez@univ-amu.fr.

Abstract

KIT is a receptor tyrosine kinase that after binding to its ligand stem cell factor activates signaling cascades linked to biological processes such as proliferation, differentiation, migration and cell survival. Based on studies performed on SCF and/or KIT mutant animals that presented anemia, sterility, and/or pigmentation disorders, KIT signaling was mainly considered to be involved in the regulation of hematopoiesis, gametogenesis, and melanogenesis. More recently, novel animal models and ameliorated cellular and molecular techniques have led to the discovery of a widen repertoire of tissue compartments and functions that are being modulated by KIT. This is the case for the lung, heart, nervous system, gastrointestinal tract, pancreas, kidney, liver, and bone. For this reason, the tyrosine kinase inhibitors that were originally developed for the treatment of hemato-oncological diseases are being currently investigated for the treatment of non-oncological disorders such as asthma, rheumatoid arthritis, and alzheimer's disease, among others. The beneficial effects of some of these tyrosine kinase inhibitors have been proven to depend on KIT inhibition. This review will focus on KIT expression and regulation in healthy and pathologic conditions other than cancer. Moreover, advances in the development of anti-KIT therapies, including tyrosine kinase inhibitors, and their application will be discussed.

KEYWORDS:

KIT; Non-oncological diseases; SCF; Tyrosine kinase inhibitors

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