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Keywords {🔍}

cell, signaling, cells, cancer, celx, breast, pubmed, test, article, lines, hsf, google, scholar, pathway, signals, egf, nrgb, cas, receptor, activity, primary, growth, data, lapatinib, fig, pertuzumab, factor, results, signal, clinical, patients, central, time, curves, human, study, line, skbr, pik, expression, inhibitor, response, activities, mdamb, tests, inhibition, additional, patient, levels, kinase,

Topics {✒️}

her2-negative/her3-high breast cancer antibody-dependent cell-mediated cytotoxicity ligand-independent her2/her3/pi3k complex targeted anti-her2 therapies triple-negative breast cancer erbb2-positive breast cancer igf-1–driven igf-1r signals igf-1–igf-1r signaling systems her2-overexpressing breast cancer nrg1b-driven her2-related signals her2-negative breast cancers article download pdf breast tumor-initiating cells diagnosing her2-driven cancer her2-breast cancer patients dysfunctional her2-driven signaling jun n-terminal kinase small-molecule kinase inhibitor abnormal her2-driven signaling ligand-driven her2 signals her2-negative patients showed 10ug/ml human insulin identify her2-negative samples her2-overexpressing cell lines node-negative tumors 1 cm her2-driven signaling activity fresh patient-derived cells ligand-driven her2 signal allowing cell-cell contacts p110alpha-selective pi3k inhibitor label-free biosensor assays mek/erk pathway inhibitor igf-1r kinase inhibitor identify her2-driven cancers ligand-receptor biosensor signals largely generated negative signalling her2-driven signaling inhibition erbb-receptor kinase family igf-1/igf-1r signals nrg1b-directed her2 signaling full size image epidermal growth factor epidermal growth factor receptor-intrinsic kinase activation anti-her2 mab biosensor-based cell assays genomic-derived biomarker correlates ligand concentration-dependent manner current fda-approved treatments

Questions {❓}

• Does lapatinib work against HER2-negative breast cancers?
• Management of Metastatic HER2-Positive Breast Cancer: Where Are We and Where Do We Go From Here?
• Relocating job wise?

Schema {🗺️}

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         headline:Development of a test that measures real-time HER2 signaling function in live breast cancer cell lines and primary cells
         description:Approximately 18–20% of all human breast cancers have overexpressed human epidermal growth factor receptor 2 (HER2). Standard clinical practice is to treat only overexpressed HER2 (HER2+) cancers with targeted anti-HER2 therapies. However, recent analyses of clinical trial data have found evidence that HER2-targeted therapies may benefit a sub-group of breast cancer patients with non-overexpressed HER2. This suggests that measurement of other biological factors associated with HER2 cancer, such as HER2 signaling pathway activity, should be considered as an alternative means of identifying patients eligible for HER2 therapies. 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. Pathway signaling is elucidated by use of highly specific agonists and antagonists. The test method relies upon well-established phenotypic, adhesion-related, impedance changes detected by the biosensor. The analytical sensitivity and analyte specificity of this method was demonstrated using ligands with high affinity and specificity for HER1 and HER3. The HER2-driven signaling quantified ranged 50-fold between the lowest and highest cell lines. The HER2+ cell lines were almost equally divided into high and low signaling test result groups, suggesting that little correlation exists between HER2 protein expression and HER2 signaling level. Unexpectedly, the highest HER2-driven signaling level recorded was with a HER2– cell line. Measurement of HER2 signaling activity in the tumor cells of breast cancer patients is a feasible approach to explore as a biomarker to identify HER2-driven cancers not currently diagnosable with genomic techniques. The wide range of HER2-driven signaling levels measured suggests it may be possible to make a distinction between normal and abnormal levels of activity. Analytical validation studies and clinical trials treating HER2- patients with abnormal HER2-driven signaling would be required to evaluate the analytical and clinical validity of using this functional biomarker as a diagnostic test to select patients for treatment with HER2 targeted therapy. In clinical practice, this method would require patient specimens be delivered to and tested in a central lab.
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         HER2-negative
         HER2-positive
         Breast cancer
         Signaling pathway
         Targeted therapeutics
         Oncology
         Breast tumor
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         Surgical Oncology
         Health Promotion and Disease Prevention
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         Medicine/Public Health
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      name:Celcuity LLC, Minneapolis, USA
      name:Celcuity LLC, Minneapolis, USA
      name:Celcuity LLC, Minneapolis, USA
      name:Division of Hematology, Oncology, and Transplantation, Departments of Medicine and Pharmacology and The Masonic Cancer Center, University of Minnesota, Minneapolis, USA
      name:Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USA
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