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Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma
Osamu Kikuchi1, Shinya Ohashi2, Tomohisa Horibe3
1Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Abstract:
Epidermal growth factor receptor (EGFR) is a key molecule in the pathophysiology of oesophageal squamous cell carcinoma (OSCC). However, EGFR-targeted agents such as anti-EGFR antibody or tyrosine kinase inhibitors for OSCC have not demonstrated any clinical benefits. Recently, a novel chemotherapeutic agent, EGFR(2R)-lytic hybrid peptide, a composite of EGFR-binding peptide and lytic peptide fragments, has been shown to exhibit a potent anti-tumour effect against cancers that express high EGFR levels. In this study, we investigated the validity of employing EGFR(2R)-lytic hybrid peptide against OSCC cells both in vitro and in vivo. Additionally, the toxicity of this peptide was assessed in mice. We found high EGFR expression levels on the cell surface of OSCC cells, and the EGFR-binding peptide fragment showed high affinity for OSCC cells. A potent cytotoxic effect was induced within 30 minutes by the exposure of OSCC cells to EGFR(2R)-lytic hybrid peptide. Furthermore, EGFR(2R)-lytic hybrid peptide markedly suppressed the tumour growth of OSCC cells in a xenograft model. Moreover, it did not cause any identifiable adverse effects in mice. Taken together, EGFR(2R)-lytic hybrid peptide was shown to be a valid therapeutic agent against OSCC, providing a crucial rationale regarding novel EGFR-targeted therapies against OSCC.
Insights
A novel EGFR(2R)-lytic hybrid peptide shows promise for treating oesophageal squamous cell carcinoma (OSCC). This agent effectively targets and eliminates OSCC cells with minimal toxicity in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Epidermal growth factor receptor (EGFR) plays a critical role in oesophageal squamous cell carcinoma (OSCC) development.
- Existing EGFR-targeted therapies have shown limited clinical efficacy in OSCC treatment.
Purpose of the Study:
- To evaluate the therapeutic potential of EGFR(2R)-lytic hybrid peptide against OSCC.
- To assess the in vitro and in vivo efficacy and toxicity of this novel peptide in OSCC models.
Main Methods:
- Investigated EGFR expression on OSCC cells.
- Assessed the binding affinity of the EGFR-binding peptide fragment to OSCC cells.
- Evaluated the cytotoxic effects of EGFR(2R)-lytic hybrid peptide in vitro.
- Determined the anti-tumour efficacy in an OSCC xenograft mouse model.
- Assessed peptide toxicity in mice.
Main Results:
- OSCC cells exhibited high surface expression of EGFR.
- The EGFR-binding peptide fragment demonstrated high affinity for OSCC cells.
- EGFR(2R)-lytic hybrid peptide induced rapid and potent cytotoxicity in OSCC cells.
- The peptide significantly suppressed OSCC tumour growth in vivo.
- No significant adverse effects were observed in mice treated with the peptide.
Conclusions:
- EGFR(2R)-lytic hybrid peptide is a promising therapeutic agent for OSCC.
- This peptide represents a novel and effective EGFR-targeted therapy strategy for OSCC.
- Preclinical data support the further development of EGFR(2R)-lytic hybrid peptide for OSCC treatment.
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