A new diagnostic test may more accurately diagnose HER2-driven breast cancer

Using ACEA Bioscience xCELLigence 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.

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.

  • "By analyzing the signaling activity in a patient’s live tumor cells, signaling abnormalities driving a cancer can be revealed that a genomic or proteomic test has not detected."
  • "The CELx HSP test has the high potential to be developed into a clinical diagnostic test or confirmatory test for better informing physicians about HER2-driven diseases such as breast cancer or HER2-driven cancer in other tissues [41, 42]. Additionally, this novel method of identification of new cancer subtypes can drive development of new drugs or repurposing of existing drugs. This tumor assessment technology may change the way personalized medicine is practiced in the future."

Citations taken from: 

A functional signal profiling test for identifying a subset of HER2-negative breast cancers with abnormally amplified HER2 signaling activity

Huang, Y., Burns, D., Rich, B., MacNeil, I., Dandapat, A., Soltani, S., Myhre, S., Sullivan, B., Furcht, L., Lange, C., Hurvitz, S., & Laing, L. (2016). A functional signal profiling test for identifying a subset of HER2-negative breast cancers with abnormally amplified HER2 signaling activity. Oncotarget, 7(48), 78577-78590. Retrieved from http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=12480

 

Figure: Representative CELx time-course curves representing a high, abnormal HER2 signaling activity in a high responder (R39) and a low HER2 signaling activity in a non-responder (R58). In this display, curves of NRG1 stimulation in the absence versus presence of pertuzumab (10 µg/mL) are presented. Retrieved from http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=12480

 

Their complete findings, published in the recent issue of the journal Oncotarget, can be viewed here (DOI: 10.18632/oncotarget.12480).

 

 

 
 

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