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EPI, Canadian Cancer Lab Look for Protein Markers Tied to Breast Cancer Metastasis

Expression Pathology and the Alberta Cancer Board’s Tom Baker Cancer Centre plan to identify protein biomarkers that can enable researchers to detect early breast cancer metastasis, the groups said last week.
Under the terms of the deal, EPI will use its tissue proteomics platform to analyze formalin-fixed, paraffin-embedded tissue samples from breast cancer patients treated at the Calgary-based Tom Baker Cancer Centre and identify protein biomarkers for early disease metastasis.
If such biomarkers are discovered, “this [project] has diagnostic and potentially drug target implications,” Peter Tunon, Expression Pathology’s VP of sales and marketing, told Pharmacogenomics Reporter this week.
The Alberta Cancer Board and Foundation, a leading funding body for collaborative cancer research in the region, has given EPI and Tom Baker a CAD$300,000 ($267,000) grant for the collaboration. Other financial terms of the alliance were not disclosed.
“This project is exactly how we see our proprietary tissue proteomics-research platform to be useful, to understand at the protein level the progression of metastasis in early-stage breast cancer,” EPI CEO Casimir Eitner said in a statement. “Our aim is to develop valuable tissue protein assays that can aid patient treatment decisions and to identify new therapeutic targets and companion diagnostics to those targets.”
The discovery process, which is slated to begin in November, will require the EPI to laser-microdissect the tissue samples with its Director Slides and Leica LMD6000 microdissector, solubilize the protein content with its Liquid Tissue MS Prep Kit, profile proteins with LC MS/MS, and identify differentially expressed proteins associated with metastasis.

“Our aim is to develop valuable tissue protein assays that can aid … treatment decisions and to identify new therapeutic targets and companion diagnostics.”

The researchers will then validate these differentially-expressed candidate proteins by immunohistochemistry at Tom Baker and by multiple-reaction monitoring mass spectrometry at EPI.
Based on the resulting findings, the collaborators will consider potential clinical commercial applications, they said.
According to Tunon, MRM analysis with EPI’s technology will enable researchers to measure multiple proteins simultaneously in FFPE tissue. “Diagnostic application may be commercialized by Liquid Tissue-based MRM analysis or by immunohistochemistry, or both, depending on the results of the project,” he said.
Although it is early days for the collaboration, Tunon suggested that the biomarkers discovered in clinical trials may even lead to a drug/diagnostic combination product.
“There is potential to identify both diagnostic biomarkers and potential new protein drug targets, and these may marry up at some point,” Tunon said. However, he stressed that “it is too early to speculate what the study results may be.”
Tunon highlighted that with EPI’s Liquid Tissue MS Prep kit, researchers will be able to use the same tissue samples both to discover and validate candidate protein markers that are believed to play a role in early-stage breast cancer metastasis.  
“One advantage of working with Liquid Tissue preps is that, using very little tissue, it is possible to generate sufficient, stable protein solution from microdissected individual patient tissue sections to provide for both discovery-stage proteomic profiling as well as downstream MRM analysis of candidate biomarkers,” Tunon said. “The same samples can be used for discovery and to verify quantitatively the differential protein expression and its relationship to the pathology reports and clinical outcomes of the patient samples studied.”
In 2008, the National Cancer Institute said that 182,460 women and 1,990 men will be diagnosed with breast cancer. This year, the NCI estimates 40,480 women and 450 men will die from the disease.
According to the NCI, approximately 61 percent of breast cancer cases are diagnosed while the cancer is still at the primary site; 31 percent are diagnosed after the cancer has spread to regional lymph nodes or directly beyond the primary site; 6 percent are diagnosed after the cancer has metastasized to other organs; while staging information is unknown for the remaining 2 percent of patients.
EPI said in a statement that it hopes its protein-based approach will “yield valuable tissue biomarkers of breast cancer metastasis as well as potential new cancer drug targets.”
“Assessment of the state of metastasis of breast cancer patients is key to optimal treatment decisions,” Anthony Magliocco, director of pathology at the Tom Baker Cancer Centre, said in a statement. “Our project with EPI will strive to identify proteins in primary tumor tissue that may serve as biomarkers of the early stages of metastasis at the molecular level.”

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