Studies from University Hospital Update Current Data on Monoclonal Antibodies (Trastuzumab emtansine is active on HER-2 overexpressing NSCLC cell lines and overcomes gefitinib resistance)
By a News Reporter-Staff News Editor at Biotech Week -- Current study results on Drugs and Therapies have been published. According to news reporting out of Parma, Italy, by NewsRx editors, research stated, "HER-2 represents a relatively new therapeutic target for non small cell lung cancer (NSCLC) patients. The incidence for reported HER-2 overexpression/amplification/mutations ranges from 2 to 20% in NSCLC."
Our news journalists obtained a quote from the research from University Hospital, "Moreover, HER-2 amplification is a potential mechanism of resistance to tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) (about 10% of cases). T-DM1, trastuzumab emtansine is an antibody-drug conjugate composed by the monoclonal antibody trastuzumab and the microtubule polymerization inhibitor DM1. The activity of T-DM1 has been studied in breast cancer but the role of T-DM1 in lung cancer remains unexplored. Antiproliferative and proapoptotic effects of T-DM1 have been investigated in different NSCLC cell lines by MTT, crystal violet staining, morphological study and Western blotting. HER-2 expression and cell cycle were evaluated by flow cytometry and Western blotting. Antibody dependent cell cytotoxicity (ADCC) was measured with a CytoTox assay. Xenografted mice model has been generated using a NSCLC cell line to evaluate the effect of T-DM1 on tumor growth. Moreover, a morphometric and immunohistochemical analysis of tumor xenografts was conducted. In this study we investigated the effect of T-DM1 in a panel of NSCLC cell lines with different HER-2 expression levels, in H1781 cell line carrying HER-2 mutation and in gefitinib resistant HER-2 overexpressing PC9/HER2cl1 cell clone. T-DM1 efficiently inhibited proliferation with arrest in G2-M phase and induced cell death by apoptosis in cells with a significant level of surface expression of HER-2. Antibody-dependent cytotoxicity assay documented that T-DM1 maintained the same activity of trastuzumab. Our data also suggest that targeting HER-2 with T-DM1 potentially overcomes gefitinib resistance. In addition a correlation between cell density/tumor size with both HER-2 expression and T-DM1 activity was established in vitro and in an in vivo xenograft model."
According to the news editors, the research concluded: "Our results indicate that targeting HER-2 with T-DM1 may offer a new therapeutic approach in HER-2 over-expressing lung cancers including those resistant to EGFR TKIs."
For more information on this research see: Trastuzumab emtansine is active on HER-2 overexpressing NSCLC cell lines and overcomes gefitinib resistance. Molecular Cancer, 2014;13():1-12. Molecular Cancer can be contacted at: Biomed Central Ltd, 236 Grays Inn Rd, Floor 6, London WC1X 8HL, England. (BioMed Central - www.biomedcentral.com/; Molecular Cancer - www.molecular-cancer.com)
Our news journalists report that additional information may be obtained by contacting D. Cretella, University Hospital Parma, Div Med Oncol, Parma, Italy. Additional authors for this research include F. Saccani, F. Quaini, C. Frati, C. Lagrasta, M. Bonelli, C. Caffarra, A. Cavazzoni, C. Fumarola, M. Galetti, S. La Monica, L. Ampollini, M. Tiseo, A. Ardizzoni, P.G. Petronini and R.R. Alfieri (see also Drugs and Therapies).
Keywords for this news article include: Parma, Italy, Europe, Antineoplastic Monoclonal Antibodies, Antineoplastics, Biotechnology, Blood Proteins, Cancer, Drugs, Drugs and Therapies, Genetics, HER2 Inhibitors, Immunoglobulins, Immunology, Medical Devices, Oncology, Therapy, Trastuzumab, Tyrosine Kinase Inhibitors
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