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Expression and role of TYRO3 and AXL as potential therapeutical targets in leiomyosarcoma

Carmela Dantas-Barbosa1, Tom Lesluyes2,3, François Le Loarer1,4

  • 1Department of Translational Research & UMR1052, CRCL, Centre Léon Bérard, 28 Rue Laennec, Lyon 69008, France.

British Journal of Cancer
|October 13, 2017
PubMed
Abstract

Insights

Targeting TAM receptors TYRO3 and AXL shows promise for advanced leiomyosarcoma (LMS). Inhibitors like crizotinib and foretinib reduced tumor cell growth and survival, suggesting potential new treatments for this rare cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Leiomyosarcoma (LMS) is a rare cancer with limited treatment options, especially in its metastatic phase.
  • TAM receptors (TYRO3, AXL) and their ligands are implicated in various cancers, including LMS.

Purpose of the Study:

  • To investigate the role of TAM receptors TYRO3 and AXL in LMS.
  • To evaluate the therapeutic potential of TYRO3 and AXL inhibitors in LMS treatment.

Main Methods:

  • Gene expression and immunohistochemistry were used to assess TAM receptor and ligand levels in LMS cell lines and patient samples.
  • TYRO3 and AXL were knocked down in LMS cells.
  • In vitro studies investigated the effects of crizotinib and foretinib on LMS cells.

Main Results:

  • LMS cells exhibited high expression of TYRO3 and AXL.
  • Knockdown of TYRO3 or AXL inhibited cell proliferation and colony formation.
  • Crizotinib and foretinib reduced TYRO3/AXL phosphorylation, induced apoptosis, and decreased colony formation.
  • Higher TYRO3 and GAS6 expression was observed in LMS compared to other sarcomas, with nuclear TYRO3 being specific to LMS.
  • High GAS6 or PROS1 expression correlated with worse progression-free survival (PFS) in LMS patients.

Conclusions:

  • LMS patients, particularly those with metastasis, show elevated TYRO3 and GAS6 levels.
  • TYRO3 and AXL inhibitors demonstrated anti-tumor activity in LMS by deactivating these pathways.
  • Clinical trials of TYRO3 and AXL inhibitors are warranted for advanced LMS.

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