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Updated: Aug 10, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
EGFR in colorectal cancer: more than a simple receptor
M Francoual1, M-C Etienne-Grimaldi, J-L Formento
1Centre Antoine-Lacassagne, Nice, France.
Background:
Advances in the understanding of tumor biology have led to the development of targeted therapies allowing progress in colorectal cancer treatment. One of the most promising targets is the epidermal growth factor receptor (EGFR).
Method:
The presence and distribution of high- and low-affinity EGFR was investigated retrospectively in a group of 82 colorectal cancer samples (43 normal colon-colon cancer paired samples) using a specific ligand binding assay (Scatchard Analysis).
Findings:
A large majority of tumor samples exhibited one class of high-affinity binding sites (78%). Eighteen cases (22%) exhibited both high- and low-affinity binding sites. A wide interpatient variability was observed for the site number, with physiologically-relevant high-affinity sites ranging from 7 to 310 fmol/mg protein in tumors and from 6 to 313 fmol/mg protein in normal mucosa. A significant positive correlation was demonstrated between tumor and normal mucosa for the high-affinity Kd values and for the number of high-affinity sites, suggesting a common regulation for both tumor and normal tissue.
Interpretation:
These observations (i) could explain recently-reported clinically-active EGFR targeting in colorectal tumors apparently negative for EGFR, and (ii) may offer a plausible explanation for the link observed between toxicity in normal tissue (cutaneous rash) and clinical outcome of patients treated with anti-EGFR drugs. Present data extends our understanding of EGFR identity in colorectal cancer which could be useful in reconsidering the predictive tools for the identification of tumors putatively responsive to EGFR targeted therapy.
Insights
This study reveals that colorectal tumors possess both high- and low-affinity epidermal growth factor receptor (EGFR) binding sites, explaining varied treatment responses and side effects in targeted cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Targeted therapies, including those targeting the epidermal growth factor receptor (EGFR), have advanced colorectal cancer treatment.
- Understanding tumor biology is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the presence and distribution of high- and low-affinity EGFR binding sites in colorectal cancer.
- To correlate EGFR expression patterns with clinical outcomes and treatment responses.
Main Methods:
- Retrospective analysis of 82 colorectal cancer samples, including paired normal colon tissue.
- Utilized a specific ligand binding assay (Scatchard Analysis) to quantify EGFR binding sites.
Main Results:
- 78% of tumor samples showed one class of high-affinity EGFR binding sites; 22% had both high- and low-affinity sites.
- Significant interpatient variability in EGFR site number was observed in both tumor and normal tissues.
- A positive correlation was found between tumor and normal mucosa for high-affinity EGFR binding characteristics, suggesting common regulation.
Conclusions:
- Findings may explain clinical efficacy of EGFR-targeted drugs in tumors with low/undetectable EGFR.
- The results offer a potential explanation for the link between anti-EGFR drug toxicity (e.g., rash) and patient outcomes.
- This research enhances the understanding of EGFR in colorectal cancer, potentially improving predictive tools for targeted therapy response.
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