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

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.

• Authors: Fusanori Yotsumoto, Satoshi Fukagawa, Kohei Miyata, Sung Ouk Nam, Takahiro Katsuda, Daisuke Miyahara, Takashi Odawara, Sadao Manabe, Toyokazu Ishikawa, Shin'ichiro Yasunaga, Shingo Miyamoto
• Journal: Anticancer research (Anticancer Res) Vol. 37 Issue 7 Pg. 3825-3831 (07 2017) ISSN: 1791-7530 [Electronic] Greece
• PMID: 28668882 (Publication Type: Journal Article)
• Copyright: Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• 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

Topics

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