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RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

Daniel V T Catenacci1, Gustavo Cervantes, Soheil Yala

  • 1University of Chicago, USA.

Cancer Biology & Therapy
|May 6, 2011
PubMed

Insights

Receptor tyrosine kinase RON (MST1R) is highly overexpressed in gastroesophageal cancer, correlating with poor survival. Targeting RON and MET together offers a promising therapeutic strategy for this disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • The MET receptor tyrosine kinase pathway is implicated in gastroesophageal cancer, yet MET inhibitors have shown limited efficacy.
  • The role and expression of RON (MST1R), a related receptor tyrosine kinase, remain poorly understood in this cancer type.

Purpose of the Study:

  • To investigate the expression, prognostic significance, and therapeutic potential of RON in gastroesophageal adenocarcinoma.
  • To explore the cooperative signaling between RON and MET and its role in resistance to MET inhibition.

Main Methods:

  • Immunohistochemistry (IHC) to assess RON expression in 94 gastroesophageal samples.
  • Quantitative PCR, FISH, and array CGH to determine MST1R gene copy number.
  • Cell line experiments to analyze RON signaling, co-stimulation with MET, and response to targeted therapies.

Main Results:

  • RON was overexpressed in 74% of samples, correlating with poor survival (p=0.008).
  • Co-expression of RON and MET (43% of samples) predicted the worst survival (p=0.03).
  • High MST1R gene copy number (35.5%) and a novel R1018G mutation (11%) were associated with poor outcomes and co-occurred with high MET/ERBB2 copy numbers.
  • RON signaling activated STAT3, enhancing cell viability; combined RON and MET inhibition was most effective in reducing tumor growth.

Conclusions:

  • RON is a significant novel prognostic marker in gastroesophageal cancer.
  • Targeting RON, particularly in combination with MET inhibition, presents a promising therapeutic strategy.
  • Further investigation of RON as a therapeutic target in gastroesophageal cancer is warranted.

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