HB-EGF Is a Promising Therapeutic Target for Lung Cancer with Secondary Mutation of EGFRT790M

Anticancer Res. 2017 Jul;37(7):3825-3831. doi: 10.21873/anticanres.11761.

Abstract

Advanced lung cancer is one of the most lethal malignancies. Many anticancer agents have been developed for lung cancer with epidermal growth factor receptor (EGFR) mutations, but its prognosis remains extremely poor. The development of molecularly-targeted therapies is required for patients with lung cancer with secondary mutation of the EGFR gene. In this study, in order to assess the validity of heparin-binding EGF-like growth factor (HB-EGF) as a therapeutic target for lung cancer with EGFR mutation, we examined the antitumor effects of a specific inhibitor (cross-reacting material 197; CRM197) on lung cancer cells with EGFR mutation. HB-EGF was the most predominantly expressed EGFR ligand in lung cancer cells with EGFR mutation. CRM197 induced significant cell apoptosis and marked suppression of tumorigenicity in lung cancer cells with single or double mutation of EGFR. These results suggest that HB-EGF is a rational target for the treatment of lung cancer with EGFR mutation.

Keywords: EGFR mutation L858 T790M; HB-EGF; lung cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Bacterial Proteins / pharmacology
  • Bacterial Proteins / therapeutic use*
  • Cell Line, Tumor
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Female
  • Gefitinib
  • Heparin-binding EGF-like Growth Factor*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Targeted Therapy
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Quinazolines / pharmacology
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Bacterial Proteins
  • Heparin-binding EGF-like Growth Factor
  • Protein Kinase Inhibitors
  • Quinazolines
  • CRM197 (non-toxic variant of diphtheria toxin)
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib