Herceptin Research Today is a free monthly online journal that collates and summarizes the latest research about Herceptin, including details on side-effects, breast cancer, treatment, therapy.

Study of inhibition effect of herceptin on interaction between Heregulin and ErbB Receptors HER3/HER2 by single-molecule force spectroscopy.

Shi X, Xu L, Yu J, Fang X

Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.

Herceptin is a monoclonal antibody against HER2, which is a member of the epidermal growth factor receptor (ErbB) family and is overexpressed in many cancers. In this work, we have applied single-molecule force spectroscopy to study the effect of Herceptin on HER2 modulated ligand-receptor interaction for ErbB signaling in living cells. Heregulin beta1 (HRG), the specific ligand of HER3, was used for HER2 activation as HER3 is the preferable dimerization partner of HER2 and HER3/HER2 is the most representative heterodimer found in cancer. Our results demonstrated a more stable binding of HRG to the cells co-expressing HER3 and HER2 than those expressing HER3 alone. Moreover, the binding force of Herceptin and HER2 is as strong as that of HRG and HER3/HER2. With the addition of Herceptin, the binding strength of HRG to the cells co-expressing HER3 and HER2 decreased. The presence of Herceptin changed the dynamic force spectrum of HRG-HER3/HER2 to that similar to HRG-HER3. Therefore, the enhancement in HRG-HER3 binding after recruiting HER2 was inhibited by Herceptin. The method offers a new approach to study the molecular mechanism of Herceptin anti-cancer effect.

Published 22 June 2009 in Exp Cell Res.
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Articles on Herceptin published 22 June 2009:

Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial.   J Clin Oncol, 27(18): 2962-9.

PURPOSE: To determine whether (1) immunohistochemical (IHC) HER2 status (ie, 2+ or 3+), (2) degree of fluorescence in situ hybridization (FISH) amplification according to (2a) HER2/CEP17 ratio or (2b) HER2 gene copy number, or (3) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy. ... [Abstract] [Full-text]

Mannose addition by yeast Pichia Pastoris on recombinant HER-2 protein inhibits recognition by the monoclonal antibody herceptin.   Vaccine.

We report here the generation of a full-length, highly glycosylated HER-2 oncoprotein using yeast strain, Pichia Pastoris. Upon treatment of secreted HER-2 with alpha-mannosidase, reactivity with the monoclonal antibody Herceptin is significantly increased. This phenomenon is due to glycosylation via mannose of the full-length HER-2 protein that extends over the antigenic epitope, which is recognized by Herceptin. The extensive glycosylation of HER-2 in Pichia Pastoris significantly increases ... [Abstract] [Full-text]

Articles on Herceptin published 18 June 2009:

Development and validation of an enzyme-linked immunosorbent assay for the quantification of trastuzumab in human serum and plasma.   Anal Biochem.

Trastuzumab, a humanized monoclonal antibody, is used for the treatment of breast cancer patients who overexpress the HER2 receptor. To optimize therapy, pharmacokinetic studies are necessary. The aim of this study was to develop an enzyme-linked immunosorbent assay (ELISA) for trastuzumab to support these pharmacokinetic studies. For this immunoassay, we raised anti-idiotype antibodies in rabbits. After purification of the rabbit material, the anti-idiotype antibodies are used as capturing ... [Abstract] [Full-text]

Articles on Herceptin published 17 June 2009:

Site specific conjugation of fluoroprobes to the remodeled Fc N-glycans of monoclonal antibodies using mutant glycosyltransferases: application for cell surface antigen detection.   Bioconjug Chem, 20(6): 1228-36.

The Fc N-glycan chains of four therapeutic monoclonal antibodies (mAbs), namely, Avastin, Rituxan, Remicade, and Herceptin, released by PNGase F, show by MALDI analysis that these biantennary N-glycans are a mixture of G0, G1, and G2 glycoforms. The G0 glycoform has no galactose on the terminal GlcNAc residues, and the G1 and G2 glycoforms have one or two terminal galactose residues, respectively, while no N-glycan with terminal sialic acid residue is observed. We show here that under native ... [Abstract] [Full-text]

Articles on Herceptin published 16 June 2009:

Estimation of hormone receptor status and HER2 in cytologic cell blocks from breast cancer using the novel rabbit monoclonal antibodies (SP1, SP2, and SP3).   Diagn Cytopathol.

The determination of estrogen (ER) and progesterone (PR) receptor status has become standard practice in the evaluation of patients with invasive breast cancer, having important prognostic and therapeutic implications. HER2 assessment is important to evaluate the response to Herceptin(R) (Trastuzumab) therapy for primary and metastatic breast cancer. This study is undertaken to compare rabbit monoclonal antibodies (RabMAb) for ER, PR, and HER2 against FDA-approved monoclonal and polyclonal ... [Abstract] [Full-text]

Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab.   Clin Cancer Res, 15(12): 4147-56.

PURPOSE: Oncogenic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is prevalent in breast cancer and has been associated with resistance to HER2 inhibitors in the clinic. We therefore investigated the combinatorial activity of GDC-0941, a novel class I PI3K inhibitor, with standard-of-care therapies for HER2-amplified breast cancer. EXPERIMENTAL DESIGN: Three-dimensional laminin-rich extracellular matrix cultures of human breast cancer cells were utilized to provide a ... [Abstract] [Full-text]

Articles on Herceptin published 15 June 2009:

Interaction between fatty acid synthase- and ErbB-systems in ovarian cancer cells.   Biochem Biophys Res Commun, 385(3): 454-9.

Fatty acid synthase (FASN) represents a metabolic oncogene. It produces phospholipids for membrane microdomains that accommodate receptor tyrosine kinases including Epidermal Growth Factor-Receptor (EGFR, ErbB1) and ErbB2 (HER2/neu). FASN and ErbBs are overexpressed in ovarian cancer. We examined the effect of FASN and ErbB inhibition on A2780 and SKOV3 ovarian cancer cells. Growth assays reveal that FASN inhibitor C75 sensitizes tumor cells against anti-ErbB drugs (pelitinib [EKB-569], ... [Abstract] [Full-text]

Target based therapies in breast cancer: current status and future perspectives.   Endocr Relat Cancer.

Identification of molecular alterations in key proteins involved in breast cancer cell proliferation and survival resulted in the development of a new treatment strategy with target based agents. The anti-ErbB-2 monoclonal antibody trastuzumab and the dual EGFR/ErbB-2 tyrosine kinase inhibitor lapatinib are effective in patients with breast cancer that overexpresses ErbB-2. The anti-VEGF-A monoclonal antibody bevacizumab is approved in combination with taxanes for treatment of unselected ... [Abstract] [Full-text]

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