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Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy
S Gattenlöhner1, B Etschmann, V Kunzmann
1Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany.
Abstract:
Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRAS(wt) genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations.
Insights
Anti-EGFR therapy does not alter KRAS/BRAF mutation status in metastatic colorectal cancer (mCRC). Analysis of 21 mCRC cases before and after treatment showed high concordance, indicating therapy resistance is not driven by these specific mutations.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anti-epidermal growth factor receptor (EGFR) targeted therapy is crucial for metastatic colorectal cancer (mCRC).
- Activating KRAS mutations predict poor response to anti-EGFR therapy, necessitating KRAS mutation analysis for patient selection.
- The impact of anti-EGFR treatment on KRAS/BRAF mutation status in recurrent mCRC remains unclear.
Purpose of the Study:
- To investigate whether anti-EGFR therapy influences KRAS/BRAF mutation status in metastatic colorectal cancer.
- To assess the concordance of KRAS/BRAF mutation status before and after anti-EGFR treatment in mCRC patients.
Main Methods:
- Analysis of KRAS/BRAF mutation status in 21 mCRC tumor samples before and after anti-EGFR therapy.
- Comparison of mutation status between pre-treatment and post-treatment samples.
- Investigation of discordant cases to identify underlying causes such as tumor mosaicism or multiple primary tumors.
Main Results:
- A high concordance (20 out of 21 cases) was observed in KRAS/BRAF mutation status before and after anti-EGFR therapy.
- One discordant case was attributed to tumor mosaicism or multiple primary tumors, not therapy-induced mutation changes.
- The findings suggest that anti-EGFR therapy does not induce alterations in KRAS/BRAF mutation status in mCRC.
Conclusions:
- Anti-EGFR therapy does not appear to influence KRAS/BRAF mutation status in metastatic colorectal cancer.
- The study provides a valuable sample set for future research into other potential anti-EGFR therapy-induced genetic alterations.
- KRAS wild-type (wt) genotype preselection remains a standard for anti-EGFR therapy in mCRC.
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