Using Cell Signaling Activity, Rather Than Biomarkers, to Determine the Optimal Therapeutic Regimen for Breast Cancer Patients

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Using ACEA Bioscience instruments, scientists at the University of Minnesota demonstrated that a functional assay of patient derived tumor cells may be a key to personalized breast cancer therapy.

The clinical classification of breast cancers is largely based upon the levels at which the patient’s cancerous cells express estrogen receptor and human epidermal growth factor receptor 2 (HER2), as determined by immunohistochemistry. Amplification of the HER2 gene and/or overexpression of the HER2 protein, which occurs in roughly 15-20% of breast cancers, is associated with more aggressive disease progression, metastasis, and a poorer prognosis. Therapeutics such as the monoclonal antibodies Trastuzumab and Pertuzumab, which bind HER2 and thereby prevent its dimerization and signaling activity, significantly improve clinical outcomes for HER2 overexpressing patients. Surprisingly, however, HER2 inhibitors have also been found to benefit some patients whose cancer cells do not overexpress HER2. It has been suggested that in these contexts it is aberrant HER2 activity, rather than increased HER2 expression, which accounts for the clinical benefit of HER2 inhibition.

In order to test the above hypothesis, Lance Laing and colleagues at the University of Minnesota have evaluated the ability of Pertuzumab to inhibit HER2-mediated signaling in breast cancer cells that do not overexpress HER2. Patient-derived malignant and healthy cells were clonally expanded and HER2 expression levels were assessed using flow cytometry. To functionally characterize HER2-mediated signaling cells were exposed to HER2 ligand and their response recorded using one of ACEA Biosciences’ xCELLigence instruments – which monitor cell number, size, and cell-substrate attachment quality in real-time using the principle of cellular impedance. HER2 stimulation by the ligand was found to rapidly increase the impedance signal (within minutes). Importantly, some primary breast cancer cells that do not overexpress HER2 still displayed a functional response to ligand stimulation. This lends support to the hypothesis that aberrant HER2 signaling in the absence of overexpression may leave some breast cancer cells still susceptible to HER2-targeted therapies. Consistent with this, the HER2 response detectable by xCELLigence could be suppressed in a dose-dependent manner by Pertuzumab. Their complete findings, published in the recent issue of the journal Oncotarget, can be viewed here.

The data from this study suggest that cell-based functional assays, as opposed to mere biomarker evaluation, may provide a more accurate means of determining the optimal therapeutic strategy for each patient. Learn more about xCELLigence RTCA and how it is being used for cancer immunotherapy research.

About xCELLigence®
ACEA’s xCELLigence® Real Time Cell Analysis (RTCA) instruments utilize gold microelectrodes embedded in the bottom of microtiter wells to non-invasively monitor the status of adherent cells using the principle of cellular impedance. In short, cells act as insulators – impeding the flow of an alternating microampere electric current between electrodes. This impedance signal is measured automatically, at an interval defined by the user (e.g. every 10 seconds, once per hour, etc.), and provides an extremely sensitive readout of cell number, cell size/shape, and cell-substrate attachment strength.

About ACEA Biosciences
Founded in 2002, ACEA Biosciences is a pioneer in the development and commercialization of high performance, cutting edge cell analysis platforms for life science research. ACEA’s xCELLigence® impedance-based, label-free, real-time cell analysis instruments and NovoCyte® flow cytometer are used in pre-clinical drug discovery and development, toxicology, safety pharmacology, and basic academic research. More than 2,000 instruments have been placed globally, leading to >1,200 peer reviewed publications.

For more information visit http://www.aceabio.com.

For further information please contact:                                                                                    
ACEA Biosciences, Inc.                                                                                                                
Dr. Jeff Xue                                                                                                                                    
Phone: +1 858 724 0928 x 3075                                                                                                
email: jxue(at)aceabio(dot)com

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Jeff Xue, Ph.D.
ACEA Biosciences, Inc.
+1 8587240928 Ext: 3075
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@aceabiosciences
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