Related Experiment Video
Updated: May 17, 2026
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Epidermal growth factor receptor: is it a feasible target for the treatment of osteosarcoma?
Jun Ah Lee1, Yunmi Ko, Dong Ho Kim
1Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea.
Purpose:
Features of epidermal growth factor receptor (EGFR) expression in osteosarcoma and in vitro efficacies of EGFR inhibitors against osteosarcoma cells were evaluated.
Materials And Methods:
Thirty biopsy samples of osteosarcoma patients were retrospectively analyzed for EGFR protein expression by immunohistochemistry. Relationships between EGFR expression and clinicopathologic characteristics and treatment outcomes were evaluated. Four osteosarcoma cell lines were analyzed for EGFR and p-EGFR expression by western blotting. Efficacies of gefitinib and BIBW2992 on osteosarcoma cells were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tyrosine kinase domains in exons 18 to 21 were sequenced and gene expression analyses of EGFR and PTEN were performed in four osteosarcoma cell lines.
Results:
EGFR protein was expressed in 27 (90%) samples (6 low, 12 intermediate, 9 high) and in three cell lines. Intermediate or high staining for EGFR was related to a tumor volume<150 mL (p<0.001) and histologic subtype other than osteoblastic type (p=0.03). However, EGFR expression was not associated with histologic response to preoperative chemotherapy or survival. Gefitinib and BIBW 2992 did not have any significant inhibitory effect on cell viabilities. DNA sequencing analysis revealed three osteosarcoma cell lines have single base changes at codon 2361 of exon 20 (G to A), without affecting translation results. Furthermore, no mutation was found to be associated with constitutive EGFR activation.
Conclusion:
In the present study, gefitinib and BIBW2992 were not effective against osteosarcoma cells. However, as osteosarcoma cells express EGFR, further studies are necessary to explore the potential of other therapeutic agents targeting EGFR.
Insights
Epidermal growth factor receptor (EGFR) is expressed in most osteosarcoma cases, but EGFR inhibitors like gefitinib showed no efficacy. Further research into other EGFR-targeting agents is needed for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a primary bone malignancy with limited treatment options.
- Epidermal growth factor receptor (EGFR) signaling pathways are implicated in various cancers.
Purpose of the Study:
- To evaluate EGFR expression in osteosarcoma.
- To assess the in vitro efficacy of EGFR inhibitors against osteosarcoma cells.
Main Methods:
- Immunohistochemistry was used to analyze EGFR protein expression in 30 osteosarcoma samples.
- Western blotting and DNA sequencing were performed on osteosarcoma cell lines.
- In vitro drug sensitivity assays were conducted using gefitinib and BIBW2992.
Main Results:
- EGFR protein was expressed in 90% of osteosarcoma samples and 3 cell lines.
- EGFR expression levels correlated with tumor volume and histologic subtype, but not with treatment response or survival.
- Gefitinib and BIBW2992 demonstrated no significant inhibitory effect on osteosarcoma cell viability.
- No activating mutations in EGFR tyrosine kinase domains were identified.
Conclusions:
- Current EGFR inhibitors (gefitinib, BIBW2992) are ineffective against osteosarcoma cells.
- Despite lack of response to tested inhibitors, EGFR expression warrants further investigation for targeted therapies.
Related Concept Videos
02:38Mitogens and the Cell Cycle
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...