Activation of AXL and antitumor effects of a monoclonal antibody to AXL in lung adenocarcinoma

Anticancer Res. 2014 Apr;34(4):1821-7.

Abstract

Background/aim: AXL (anexelekto) has been explored as a potential novel therapeutic target for non-small cell lung carcinoma (NSCLC) but its activation status has not been evaluated in NSCLC.

Patients and methods: We first immunolocalized the phosphorylated form of AXL in 112 lung adenocarcinoma cases and subsequently evaluated the anti-neoplastic effects of monoclonal antibody AXL in two lung adenocarcinoma cell lines, PC9 and A549.

Results: Phospho-AXL immunoreactivity was detected in 59.8% of adenocarcinoma cases examined and tended correlate significantly with larger tumor size (p=0.08) and with overall survival of the patients (p=0.041). Results of in vitro analysis revealed that the monoclonal antibody to AXL significantly inhibited cell proliferation of PC9 and A549, lung adenocarcinoma cell lines, which was caused by an inhibition of extracellular signal-regulated kinase (ERK) activation.

Conclusion: AXL-targeted therapy, possibly through inhibiting ERK activation of carcinoma cells, could confer clinical benefits on patients with lung adenocarcinoma.

Keywords: AXL; lung adenocarcinoma; monoclonal antibody therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Aged
  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Axl Receptor Tyrosine Kinase
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Enzyme Activation / drug effects
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Phosphorylation
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Tumor Burden

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human