Recently, HER2-directed treatment, such as trastuzumab, has shown clinical benefit in HER2-amplified gastric cancer. On the basis of recent studies about epidermal growth factor receptor (EGFR) or HER2targeting agents (including gefitinib, lapatinib, and trastuzumab) in gastric cancer, the potent effects of pan-HER inhibitors targeting the HER family are anticipated. In this study, we evaluated...

Approximately, 25-30% of early-stage breast tumors are classified at the molecular level as HER2-positive, which is an aggressive subtype of breast cancer. Amplification of the HER2 gene in these tumors results in a substantial increase in HER2 mRNA levels, and consequently, HER2 protein levels. HER2, a transmembrane receptor tyrosine kinase (RTK), is targeted therapeutically by a monoclonal an...

Since the initial description of the HER2 proto-oncogene as a poor prognostic factor in breast cancer in 1987, to the first randomized trial of a monoclonal antibody directed against HER2 in combination with chemotherapy for the treatment of metastatic HER2-positive breast cancer published in 2001, to the American Society of Clinical Oncology (ASCO) 2005 Annual Meeting in which we saw the unpre...

Protein-protein interactions are harder to target by small organic molecules than by enzymes or nuclear hormone receptors. Here we report the discovery of an organic compound that inhibits the expression of the Her2 oncogene by disrupting an alpha-helix-mediated protein interaction. The druglike molecule we named adamanolol competitively inhibited the interaction between the two cancer-linked n...

The receptor tyrosine kinase Her2, an intensely pursued drug target, differs from other members of the EGFR family in that it does not bind EGF-like ligands, relying instead on heterodimerization with other (ligand-bound) EGFR-family receptors for activation. The structural basis for Her2 heterodimerization, however, remains poorly understood. The unexpected recent finding of asymmetric ectodom...

BACKGROUND The purpose of this study was to assess the clinical relevance of HER2 amplification by a novel chromogenic in situ hybridisation (CISH) technique in patients with primary breast cancer and to determine its relationship with other prognostic markers. MATERIALS AND METHODS One hundred and seventy-three breast cancer patients with a mean follow-up duration of 75 months were reanalyse...

Approximately 20%-25% of all breast cancers over express a key cell surface growth factor receptor known as HER2. HER2 plays a key role in cell growth and proliferation and is linked to worse clinical outcomes, making it a logical therapeutic target. The first HER2 targeted drug to be approved by the FDA, was the humanized monoclonal antibody trastuzumab, after it showed improvements in surviva...

BACKGROUND Trastuzumab (Herceptin), an anti-HER2/neu receptor monoclonal antibody that inhibits growth of ErbB2-overexpressing breast cancer, is used to treat such cancers. Development of resistance to trastuzumab, however, is common. We investigated whether insulin-like growth factor-I (IGF-I), which activates cell survival signals, interferes with the growth-inhibitory action of trastuzumab. ...

HER2 amplification is found in more than 15% of gastric cancers and is associated with poor clinical outcome. Lapatinib, a dual HER2 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown promising in vitro results in treating HER2(+) cancer cells. However, several studies have shown that activation of alternative receptor tyrosine kinases can mediate resistance to HER...

We describe the construction and characterization of an Ab fusion protein specific for the tumor-associated Ag HER2/neu linked to sequences encoding the extracellular domain of the B7.1 T cell costimulatory ligand. The Ab domain of the fusion molecule will specifically target HER2/neu-expressing tumor cells, while the B7.1 domain is designed to activate a specific immune response. We show that ...