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.
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.
Authors: Molly E Heft Neal; Andrew C Birkeland; Apurva D Bhangale; Jingyi Zhai; Aditi Kulkarni; Susan K Foltin; Brittany M Jewell; Megan L Ludwig; Lisa Pinatti; Hui Jiang; Jonathan B McHugh; Lawence Marentette; Erin L McKean; J Chad Brenner Journal: BMC Cancer Date: 2021-05-29 Impact factor: 4.430