AXL: A novel therapeutic target in IBD

Adv Pharmacol. 2024:101:141-157. doi: 10.1016/bs.apha.2024.10.009. Epub 2024 Oct 22.

Abstract

Inflammatory bowel diseases (IBD) and their sequela (colitis-associate carcinoma and fibrostenotic complications) remain a significant clinical challenge and novel therapeutic targets are desperately needed. AXL, a receptor tyrosine kinase, has been implicated in myriad cellular functions central to the pathogenesis of IBD. These include facilitating epithelial-to-mesenchymal transition, dampening of Toll-like receptor and natural killer cell mediated immune responses, driving proliferation, and propagating fibrogenic signaling. The vast majority of preclinical research on AXL has focused on its role in cancer. As such, pharmacologic AXL inhibitors are currently in clinical trials, but the indications remain limited to malignancy. In this chapter, we summarize the current preclinical data of AXL in IBD, colitis associated carcinoma, and fibrostenotic disease, and highlight its potential as a novel therapeutic target.

Keywords: AXL; Crohn's disease; IBD; Intestinal fibrosis; Tyrosine kinase.

Publication types

  • Review

MeSH terms

  • Animals
  • Axl Receptor Tyrosine Kinase*
  • Colitis-Associated Neoplasms / drug therapy
  • Colitis-Associated Neoplasms / metabolism
  • Colitis-Associated Neoplasms / pathology
  • Humans
  • Inflammatory Bowel Diseases* / drug therapy
  • Inflammatory Bowel Diseases* / metabolism
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins* / antagonists & inhibitors
  • Proto-Oncogene Proteins* / metabolism
  • Receptor Protein-Tyrosine Kinases* / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases* / metabolism

Substances

  • Axl Receptor Tyrosine Kinase
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Protein Kinase Inhibitors