Human epidermal growth factor receptor 2 (ErbB2) amplification and overexpression has been seen in many cancer types including non-small cell lung cancer (NSCLC).
ERBB2/HER2/NEU, a member of the epidermal growth factor receptor family, is overexpressed in more than 25 % of non-small cell lung cancer and is considered to be a significant and independent prognostic factor in lung cancer.
By FACS, we found Her-2/neu overexpression (mean fluorescence intensity >8) in 2 of the 22 non-small cell lung cancer (NSCLC) cell lines (9%), none of 11 small cell lung cancer (SCLC) cell lines, and 4 of 5 breast cancer cell lines.
The effects of lapatinib on the proliferation of human NSCLC tumor cell lines expressing wild-type or variant EGFR and HER2cannot be explained solely on the basis of the biochemical activity or receptor autophosphorylation in recombinant cells.
Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation.
We elected to see if the extra cellular domain of HER-2/neu, the p 105 fraction, which is found in the circulation, has any regulatory influence on uPA or uPAR in those patients with NSCLC Levels of uPA, uPAR and p 105 HER-2/neu were determined in blood from age-matched controls and patients with advanced NSCLC.
Thus, a prospective analysis of the co-expression of Bcl-2 + HER2 in NSCLC patients may identify patients with a poor prognosis who may benefit from more aggressive therapy.
In addition, afatinib, a small molecule kinase inhibitor that causes irreversible inhibition of EGFR (epidermal growth factor receptor) and HER2, was recently approved for EGFR-mutated non-small cell lung cancer.
NSCLC cell lines (H460, H358, H322, or H661) were assayed for expression of erbB1 and erbB2, the cell adhesion molecule E-cadherin, secretion of the matrix metalloproteinase 9 (MMP-9), and vascular endothelial cell growth factor (VEGF), as well as their ability to invade Matrigel after 48-hour exposure to 17AAGA.
Afatinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been approved as EGFR, HER2, HER3 and HER4 inhibitor for non-small cell lung cancer (NSCLC) treatment.
HER2 gene copy numbers per cell were evaluated by fluorescent in situ hybridization (FISH) in 102 NSCLC patients treated with gefitinib, and previously evaluated for EGFR status by FISH, immunohistochemistry, and presence of mutations.
Using a panel of 20 non-small cell lung cancer (NSCLC) cell lines established from previously untreated patients, we investigated the relationships between intrinsic chemoresistance (to four agents used commonly in the therapy of NSCLC) and HER-2/neu gene expression (which encodes glycoprotein p185neu), p53 gene mutations, and cell proliferation characteristics.
Considering that osimertinib can lead to enhanced HER-2 expression on cell surface and HER-2 overexpression is a mechanism of resistance to osimertinib, this study was addressed to investigate the potential of combining osimertinib with trastuzumab emtansine (T-DM1) in order to improve the efficacy of osimertinib and delay or overcome resistance in NSCLC cell lines with EGFR activating mutation and with T790M mutation or HER-2 amplification.
In conclusion, the expression screening of PTPs in lung cancer reported here has identified PTPN13 as a novel candidate tumor suppressor in NSCLC whose loss increases signaling from epidermal growth factor receptor and HER2 tyrosine kinase receptors.