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Targeting the receptor tyrosine kinase MerTK shows therapeutic value in gastric adenocarcinoma

Naita Maren Wirsik1,2, Mingyi Chen1, Liping He1

  • 1Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.

Cancer Medicine
|March 28, 2024
PubMed
Abstract

Insights

High MerTK expression indicates poor survival in gastric cancer. Inhibiting MerTK (Mer tyrosine kinase) shows promise as a new treatment, improving survival and overcoming chemotherapy resistance in advanced tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Gastric adenocarcinoma has poor patient survival rates, particularly in advanced stages.
  • The role of Mer tyrosine kinase (MerTK) in gastric cancer is not well understood.
  • Existing therapies offer limited efficacy for advanced gastric adenocarcinoma.

Purpose of the Study:

  • To investigate the prognostic value of MerTK in gastric adenocarcinoma.
  • To evaluate the therapeutic potential of MerTK inhibition in gastric cancer models.
  • To explore MerTK's role in treatment resistance.

Main Methods:

  • Immunohistochemistry analyzed MerTK expression in 140 gastric adenocarcinoma patients.
  • CRISPR/Cas9 and siRNA were used to knock out/down MerTK in gastric cancer cell lines.
  • In vitro and in vivo models assessed cell proliferation, migration, invasion, and xenograft tumor growth.
  • The MerTK inhibitor UNC2025 was evaluated in vitro and in vivo.

Main Results:

  • High MerTK expression correlated with decreased overall survival and lymph node metastasis, especially without neoadjuvant therapy.
  • MerTK knockout/knockdown reduced cancer cell proliferation and migration in vitro and in vivo.
  • The MerTK inhibitor UNC2025 demonstrated significant therapeutic effects.
  • MerTK inhibition sensitized gastric cancer cells to 5-Fluorouracil (5-FU) chemotherapy.

Conclusions:

  • MerTK serves as a potential prognostic biomarker for gastric adenocarcinoma.
  • Targeting MerTK offers a novel therapeutic strategy for advanced gastric cancer.
  • MerTK inhibition may overcome resistance to standard chemotherapies, including 5-FU.
Keywords:
MerTKUNC2025chemotherapygastric adenocarcinomasurvival

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