A Big Barrier to Cancer Genomic Sequencing

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cp418
cp418 Member Posts: 7,079
edited June 2014 in Clinical Trials, Research News, Podcasts, and Study Results

http://boards.medscape.com/forums?128@872.CNbdaIeBheB@.2a342d7d!comment=1

A Big Barrier to Cancer Genomic Sequencing

Eric Topol, MD: Director, Scripps Translational Science Inst.

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  • gpawelski
    gpawelski Member Posts: 564
    edited August 2012

    Cell Lines vs Fresh Cells

    The pathologist establishes a cell-line (immortalizes it) with your tumor cells. A cell-line is a product of immortal cells that are used for biological research. Cell lines can perpetuate division indefinitely. Regular cells can only divide approximately 50 times.

    Cell lines are useful for experimentation in labs as they are always available to researchers as a product and do not require harvesting (acquiring of tissue from a host) every time cells are needed in the lab.

    Problem is, cell lines don't recapitulate drug response patterns which exist in the body. For drug selection, it is better to directly remove tumor microclusters straight from the body and immediately test them, before they change.

    There is the issue about cell-lines vs fresh cells. Cell-lines have always played, and continue to play, an important role in drug screening and drug development.

    The problem is that cell-lines do not predict for disease or patient specific drug effects. If you can kill ovarian cancer cell-lines with a given drug, it doesn't tell you anything about how the drug will work in real world, clinical ovarian cancer (real-world conditions). But you can learn certain things about general drug biology through the study of cell lines.

    As a general rule, studies from established cell-lines (tumor cells that are cultured and maniplated so that they continue to divide) have proved worthless as models to predict the activity of drugs in cancer. They are more misleading than helpful. An established cell-line is not reflective of the behavior of the fresh tumor samples (live samples derived from tumors) in primary culture, much less in the patient.

    Established cell-lines have been a huge disappointment over the decades, with respect to their ability to correctly model the disease-specific activity of new drugs. What works in cell-lines do not often translate into human beings. You get different results when you test passaged cells compared to primary, fresh tumor.

    Research on cell-lines is cheap compared to clinical trials on humans. One gets more accurate information when using intact RNA isolated from "fresh" tissue than from using degraded RNA, which is present in paraffin-fixed tissue.

    My thoughts would be, do you want to utilize your tissue specimen for "drug selection" against "your" individual cancer cells or for mutation identification, to see if you are "potentially" susceptible to a certain mechanism of attack.

    In the later, there are many laboratories that commercially offer analyses. These gene array methods can be automated and conducted comparatively cheaply.

    In the former, some labs have not pursued genomics because cancer is more complex than its gene signature. Contained within the genes of each human is the information to create every protein, every enzyme, every lipid, every carbohydrate and all the organs and systems dependant upon their function.

    What is not known is how all of those 25,000+ genes are regulated to produce the unique features that constitute us as human beings.

    By studying human cellular behavior within the context of vascular, stromal and inflammatory elements, the functional profiling platform provides the closest approximation of human biology, short of possibly a clinical trial.

    Cell Function Analysis 

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  • gpawelski
    gpawelski Member Posts: 564
    edited August 2012

    Will the Real Cancer Cell Please Stand Up?

    In a recent article in Biotechniques, "Will the Real Cancer Cell Please Stand Up," it seems that cancer cells are not individual entities but networks. A harmonic oscillation develops between tumor, stroma, vasculature and cytokines. In this mix, the cancer cell is but one piece of the puzzle. The value of using cancer cell lines for drug sensitivity investigation has recently come under fire.

    According to research work at Baylor, some of the tumor promotion signals in the form of small interfering RNAs, may arise not from the cancer cells, but instead from the surrounding stroma. How then will even genomic analyses of cancer cells play out in the real world of human tumor biology and clinical response prediction?

    Not very well, according to Dr. Robert Nagourney, Medical and Laboratory Director, Rational Therapeutics, Inc., Long Beach, California. The technology is so complex as to be beyond the ken of both patients and physicians alike. Thus, expertise is required and that expertise is provided by those engaged in the field. The utility of drug selection is beyond reproach.

    Scientifically interesting technology has been brought to the market. It exists to meet an unmet need. What is lacking, however, is evidence. Not necessarily evidence in the rarefied Cochrane sense of idealized survival curves, nor even Level II evidence, but any evidence at all. Dr. Nagourney fears a lack of competent due diligence.

    The best medicine comes from treating the right patient with the right therapy at the right time. And while that seemingly simple prescription rings true, the path to the three Rs of medical treatment is anything but simple and straightforward—especially in treating the multiplicity of cancers. As scientists struggle to decode and decipher the mountain of cancer cell genomic data currently—or soon to be—available, knowing which data set correctly describes a tumor’s inner workings, is a huge challenge. Such is the case with research on established cancer cell lines as opposed to cells derived directly from a patient’s tumor.

    Cancer cell lines date back to the 1950s, when the first line was established from a woman with cervical cancer named Henrietta Lacks. In the decades since, approximately 1000 cancer cell lines have become essential tools for cancer cell biology and to test drugs. Indeed, almost every anti-cancer drug now in use gained early traction through testing on cancer cell lines. But now some researchers are calling for new models that can assay primary cancer cells directly from patients to sketch a more realistic molecular portrait of primary tumors.

    http://www.biotechniques.com/news/Will-the-Real-Cancer-Cell-Please-Stand-Up/biotechniques-329467.html 

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