Pathway signaling is elucidated by use of highly specific agonists and antagonists. ANA KULI] 2. In healthy cells, HER2 activation triggers signaling pathways that control normal cell growth, differentiation, motility, and adhesion. Cold Spring Harbor, NY — One of the most promising ideas in cancer treatment is to apply a lesson learned in the fight against AIDS (Acquired Immune Deficiency Syndrome): simultaneously attacking a pathological process at different points of weakness can, in some cases, … New signaling pathway discovered in HER2-positive breast cancer, and two potentially powerful drug targets. New signaling pathway discovered in HER2-positive breast cancer, and 2 powerful drug targets Mammary epithelial cells grow in clusters called acini. Dimerization of the receptor results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways leading to cell proliferation and tumorigenesis. Molecular profiling of HER2 signaling of a large cohort of human breast cancer specimens using a quantitative and sensitive functional pathway activation mapping technique reveals IHC(-)/FISH(-)/pHER2(+) tumors with HER2 pathway activation independent of total HER2 levels and functional signaling … Using gene expression profiling, it could be shown that these differences in signaling magnitude and duration translate into distinct responses at the transcriptome level. Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. In these cells, both ligands signal through an ErbB2/ErbB3 heterodimer, leading to the activation of the same subset of downstream pathways but with differing signaling kinetics. For this reason, the HER2 signaling pathway is a target of significant interest for cancer researchers. DAMIR VRBAN EC 1, 2. Overexpression of HER2 leads to the over-activation of downstream pathways, including the PI3K/Akt/mTOR and MAPK/ERK signaling cascades, which are known to be involved in malignant transformation [ 35 ] . HER2 signaling pathway is a complex network comprised of mem-b rane receptor and their ligands, protein kinases and regulating genes. Conclusions: Molecular profiling of HER2 signaling of a large cohort of human breast cancer specimens using a quantitative and sensitive functional pathway activation mapping technique reveals IHC−/FISH−/pHER2+ tumors with HER2 pathway activation independent of total HER2 levels and functional signaling through HER3 and EGFR. When HER2 signaling is activated, the clusters -- which normally have hollow centers -- assume an irregular, or dysplastic form (left). HER2 signaling pathway is a complex network comprised of mem-brane receptor and their ligands, protein kinases and regulating genes NATALIJA DEDI] PLAVETI]1 ANA KULI] 2 DAMIR VRBANEC 1, 2 1 Department of Medical Oncology, Division of Oncology University Hospital Center and Zagreb EGFR-HER2 heterodimers similarly evade endocytic degradation in favor of the recycling pathway and have increased signaling duration and potency (Lenferink et … NAT ALIJA DEDI] PLAVETI] 1. A new biosensor-based test (CELxTM HSF) that measures HER2 signaling activity in live cells is demonstrated using a set of 19 human HER2+ and HER2– breast cancer reference cell lines and primary cell samples derived from two fresh patient tumor specimens.