HB-EGF inhibition in combination with various anticancer agents enhances its antitumor effects in gastric cancer
Ayako Sanui1, Fusanori Yotsumoto, Hiroshi Tsujioka
1Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Abstract:
Advanced gastric cancer (GC) is one of the most lethal malignancies. Although many anticancer agents exist for the treatment of GC, its prognosis remains extremely poor. Therefore, further development of targeted therapies is required for patients with GC. To assess the role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) as a target for GC therapy, the expression of EGF receptor ligands in GC cell lines, and the antitumor effects of an HB-EGF inhibitor (CRM197) as a single agent and in combination with other anticancer agents was assessed in GC cells. HB-EGF was the predominantly expressed ligand among EGF receptor ligands in all the cells. CRM197 induced significant cell apoptosis. Anticancer agents augmented the secretion of HB-EGF into the medium and simultaneously induced cell apoptosis. Combination of CRM197 with other anticancer agents significantly enhanced cell apoptosis. Additionally, co-administration of CRM197 and paclitaxel resulted in synergistic antitumor effects. These results suggested that HB-EGF is a rational target for GC therapy.
Insights
Targeting heparin-binding epidermal growth factor-like growth factor (HB-EGF) with CRM197 shows promise for advanced gastric cancer (GC) therapy. Combining CRM197 with other agents significantly enhances antitumor effects and apoptosis in GC cells.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Advanced gastric cancer (GC) presents a significant clinical challenge with poor prognosis despite available treatments.
- Development of targeted therapies is crucial for improving outcomes in GC patients.
- Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is implicated in cancer progression.
Purpose of the Study:
- To evaluate the expression of epidermal growth factor receptor (EGFR) ligands in GC.
- To assess the therapeutic potential of the HB-EGF inhibitor CRM197 in GC.
- To investigate the combined effects of CRM197 with other anticancer agents.
Main Methods:
- Analysis of EGFR ligand expression in GC cell lines.
- Treatment of GC cells with CRM197 as a single agent and in combination therapy.
- Assessment of cell apoptosis and antitumor effects.
Main Results:
- HB-EGF was identified as the predominant EGFR ligand in GC cells.
- CRM197 treatment induced significant apoptosis in GC cells.
- Combination therapy with CRM197 and other anticancer agents, including paclitaxel, enhanced apoptosis and demonstrated synergistic antitumor effects.
Conclusions:
- HB-EGF represents a rational therapeutic target for advanced gastric cancer.
- CRM197, an HB-EGF inhibitor, exhibits potential as a single agent and in combination therapies for GC.
- Combination strategies involving CRM197 may improve treatment efficacy for gastric cancer.
Related Concept Videos
Mitogens and the Cell Cycle
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Combined Effects of Drugs: Synergism
Such synergistic combinations...
Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
