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Published on: May 20, 2020
Lack of somatic ErbB2 tyrosine kinase domain mutations in hepatocellular carcinoma
Chiung-Ing Wong1, Hui-Ling Yap, Seng-Gee Lim
1Department of Haematology-Oncology and Gastroenterology, National University Hospital, Singapore.
Aim:
Small molecules targeting the epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain have shown promising activity in cancer therapeutics. Recent reports suggest activity of erlotinib, an ErbB1 inhibitor, and lapatinib, a dual inhibitor of ErbB1 and ErbB2, in hepatocellular carcinoma (HCC). Activating ErbB1 somatic mutations may predict treatment responses.
Method And Results:
We have previously reported ErbB1 tyrosine kinase domain mutations to be rare or absent in HCC, but data on the frequency of ErbB2 tyrosine kinase domain mutations in HCC is currently limited, apart from reports of a missense mutation identified in 11% of a small Caucasian sample. We studied exons 18-23 of the ErbB2 gene from tumor DNA of 100 Asian human HCC and found no exonic mutations of potential significance.
Conclusion:
Alternative mechanisms may be responsible for the observed therapeutic efficacy of ErbB1 and ErbB2 tyrosine kinase inhibitors.
Insights
Epidermal growth factor receptor (EGFR) inhibitors show promise in hepatocellular carcinoma (HCC) treatment. However, this study found no significant ErbB2 mutations in Asian HCC patients, suggesting alternative treatment mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Small molecule inhibitors targeting the epidermal growth factor receptor (EGFR) tyrosine kinase domain are effective cancer therapeutics.
- Erlotinib (ErbB1 inhibitor) and lapatinib (dual ErbB1/ErbB2 inhibitor) have shown potential in hepatocellular carcinoma (HCC).
- Activating somatic mutations in EGFR may predict treatment response.
Purpose of the Study:
- To investigate the frequency of ErbB2 tyrosine kinase domain mutations in Asian HCC.
- To explore potential mechanisms of action for EGFR and ErbB2 inhibitors in HCC.
Main Methods:
- Analysis of exons 18-23 of the ErbB2 gene in tumor DNA from 100 Asian HCC patients.
- Review of previous findings on ErbB1 mutations in HCC.
Main Results:
- ErbB1 tyrosine kinase domain mutations are rare or absent in HCC.
- No exonic mutations of potential significance were found in the ErbB2 gene in the studied HCC cohort.
- Previous studies reported a missense ErbB2 mutation in 11% of a small Caucasian HCC sample.
Conclusions:
- The observed therapeutic efficacy of ErbB1 and ErbB2 tyrosine kinase inhibitors in HCC may involve mechanisms beyond direct mutations in these genes.
- Further research is needed to elucidate the precise mechanisms driving the response to these targeted therapies in HCC.
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