Expression Pathology Aids Research In Identifying Biomarkers Of Lung Cancer Metastasis And Survival
Main Category: Lung CancerAlso Included In: Cancer / Oncology
Article Date: 21 Feb 2008 - 1:00 PDT
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Expression Pathology Inc. (EPI), a leader in tissue proteomics, announced that researchers at Tokyo Medical University, using the company's tissue microproteomics technologies, identified protein biomarkers associated with lung cancer metastasis, which were further studied for correlation to clinical outcomes. The researchers used EPI's Liquid Tissue® reagents and Director™ laser microdissection slides to analyze formalin-fixed paraffin-embedded (FFPE) tissue samples by mass spectrometry.
"A novel combination of technologies has enabled proteomic discovery and analysis of previously unusable archived tissue, first in a semi-quantitative manner and then in a more targeted way to focus on specific individual proteins," said Professor Toshihide Nishimura of Tokyo Medical University and a scientific advisor to EPI. "We were able to take the same Liquid Tissue processed samples used in discovery and measure the relative expression of candidate biomarkers with recent advances in Multiple Reaction Monitoring. We have demonstrated their potential utility as indicators of the stage of disease and predictors of patient survival."
A white paper detailing the methodology and results of the research to date is available from Expression Pathology; for a complimentary download, visit http://www.expressionpathology.com.
"FFPE tissue archives represent an extraordinary resource for mining protein biomarkers associated with differential clinical outcomes," said David Krizman, PhD, EPI's Chief Scientific Officer. "However, detailed proteomic analysis by mass spectrometry of specific cellular features of these samples has, until recently, not been feasible."
"This study clearly demonstrates how Expression Pathology's Liquid Tissue MS Protein Prep and Director slides have opened archived tissue to discovery and validation of protein biomarkers of differential pathologies and clinical outcomes," Dr. Krizman continued.
About Expression Pathology Inc.
Formalin-fixed and paraffin-embedded (FFPE) tissue samples are routinely collected and stored in medical treatment and research facilities. They constitute a huge untapped resource for discovery, validation and accurate measurement of biomarkers of disease progression and recurrence, drug response and toxicity. Expression Pathology's Liquid Tissue® reagents and Director™ laser microdissection slides are opening new ways to extract valuable protein information from FFPE tissue, and could provide the foundation for a new generation of clinical research and diagnostic tools.
Expression Pathology Inc.
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Predicting Lung Cancer Patient Response To Therapy
posted by Gregory D. Pawelski on 23 Feb 2008 at 8:27 amThe drug discovery model over the last few years has been limited to one gene or protein, one target, one drug. The "cell" is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems' response to drug treatments, not just one target or pathway.
Genetic profiles are able to help doctors determine which patients will probably develop cancer, and those who will most likely relapse. However, it cannot be suitable for specific treatments for "individual" patients.
Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes. Targeting one pathway may not be as effective as targeting multiple pathways in a cancer cell.
Another challenge is to identify for which patients the targeted treatment will be effective. Tumors can become resistant to a targeted treatment, or the drug no longer works, even if it has previously been effective in shrinking a tumor. Drugs are combined with existing ones to target the tumor more effectively. Most cancers cannot be effectively treated with targeted drugs alone.
The key to understanding the genome is understanding how cells work. The ultimate driver is a "functional" assay (is the cell being killed regardless of the mechanism) as opposed to a "target" assay (does the cell express a particular target that the drug is supposed to be attacking). While a "target" assay tells you whether or not to give "one" drug, a "functional" assay can find other compounds and combinations and can recommend them from the one assay.
The core of the functional assay is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a "targeted" drug could perturb any one of these pathways, it is important to examine the effects of the drug within the context of the cell. Both genomics and proteomics can identify potential new therapeutic targets, but these targets require the determination of cellular endpoints.
Cell-based "functional" assays are being used for screening compounds for efficacy and biosafety. The ability to track the behavior of cancer cells permits data gathering on functional behavior not available in any other kind of assay.
Protein biomarkers, important in order to identify new therapeutic targets and thereby to develop useful drugs, are still years away from working successfully in predicting treatment response for "individual" patients. Perhaps this is because they are performed on dead, preserved cells that were never actually exposed to the drugs whose activity they are trying to assess.
The cell "function" methodology, which exists today and is not hampered by the problems associated with expression tests. That is because the cell-based profiling measures the net effect of all processes within the cancer, acting with and against each other in real time, and it tests "living" cells actually exposed to drugs and drug combinations of interest.
Literature Citation: Eur J Clin Invest 37 (suppl. 1):60, 2007
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