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Human epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma
Yoko Takahashi1, Junegoo Lee1, Curtis Pickering1
1Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Background:
Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite multimodal therapy, the prognosis in SNUC remains poor, and new therapies are needed. Thus, the purpose of this study was to explore potential therapeutic targets in SNUC.
Methods:
Using the human-derived SNUC MDA8788-6 cell line, we performed whole genome single nucleotide polymorphism (SNP) analysis to identify copy number changes in this line. Protein expression levels were evaluated by Western blotting. Cell growth inhibition was assessed by methylthiazol tetrazolium (MTT) and clonogenic assays. The mouse flank model was used to examine the effect of growth inhibition in vivo.
Results:
The ERBB2 gene was highly amplified and cell extracts showed human epidermal growth factor receptor 2 (HER2) was overexpressed and phosphorylated in MDA8788-6. Lapatinib effectively inhibited the HER2 signaling pathway in our SNUC cell line. HER2 inhibition successfully suppressed the cell growth of MDA8788-6 cells both in vitro and in vivo.
Conclusion:
Targeting HER2 may be a promising avenue for the development of novel therapies for SNUC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1926-E1934, 2016.
Insights
Targeting human epidermal growth factor receptor 2 (HER2) shows promise for treating sinonasal undifferentiated carcinoma (SNUC). Inhibiting HER2 effectively suppressed SNUC cell growth in laboratory and animal models, suggesting new therapeutic strategies.
Area of Science:
- Oncology
- Cancer Biology
- Genetics
Background:
- Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy with a poor prognosis despite current treatments.
- There is a critical need for novel therapeutic strategies to improve outcomes for SNUC patients.
Purpose of the Study:
- To identify potential therapeutic targets in SNUC.
- To investigate the role of ERBB2/HER2 signaling in SNUC.
Main Methods:
- Whole genome single nucleotide polymorphism (SNP) analysis of the SNUC MDA8788-6 cell line to detect copy number alterations.
- Western blotting to assess protein expression levels.
- In vitro (MTT and clonogenic assays) and in vivo (mouse flank model) studies to evaluate the effects of HER2 inhibition on cell growth.
Main Results:
- The ERBB2 gene was found to be highly amplified in the SNUC cell line.
- Overexpression and phosphorylation of human epidermal growth factor receptor 2 (HER2) were confirmed.
- Lapatinib, an HER2 inhibitor, effectively suppressed SNUC cell proliferation both in vitro and in vivo.
Conclusions:
- Targeting HER2 represents a promising therapeutic strategy for sinonasal undifferentiated carcinoma.
- HER2 signaling pathway inhibition warrants further investigation for SNUC treatment development.
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