Multiplex Proteomic Analysis of Cells in Fine Needle Aspiration Samples: How Soon Can We Expect to Individualize Therapy by Comparing Pre- and Posttreatment Biopsies?

Individualized therapy of the future will be guided by panels of biomarkers that include proteins, nucleic acids, and metabolites. Among these analyte classes, proteins can provide direct functional information central to the disease. The added bonus is that the protein, or phosphoprotein, biomarker is the drug target itself and/or the direct readout of the signaling activity being inhibited. An example is the selection of kinase inhibitor therapy based on phosphorylated receptor tyrosine kinases, such as human epidermal growth factor receptor 2, protein kinase B, epidermal growth factor receptor, MET receptor tyrosine kinase, or cytoplasmic signaling proteins, such as mammalian target of rapamycin. Yet it has not been easy to quantitatively measure a panel of protein/phosphoprotein biomarkers in tissue biopsy samples with high precision, sensitivity, and accuracy, which are essential attributes if the data are used to select patient therapies. Addressing this challenge, Ullal et al. (1) described a new technology that uses DNA barcode labeling of antibodies for multiplex proteomic/phosphoprotein analysis of cells in a tumor fine needle aspiration (FNA).2 FNAs are challenging clinical specimens that contain relatively few cells compared to a tissue biopsy. Why is this method important, how does it compare to existing multiplexed clinical proteomic technologies, and when can we hope to see this platform routinely used in the clinical laboratory?The author's platform (1) is divided into serial stages. In the first stage, the cells are passed through a microfluidic chamber where tumor cells are separated from host cells. Here, the cell mixture is exposed to antibodies tagged with magnetic particles. This permits the removal of contaminating immune cells or positive selection of tumor cells. In the second stage, the cancer cells are incubated with a cocktail of antibodies that are labeled with DNA “barcodes.” Each barcode is a different 70-nucleotide sequence. The DNA …