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Jan 15, 2010 (Vol. 30, No. 2)

Cancer Biomarker Chase Accelerates

Researchers Are Rapidly Gaining Ground in the Identification of These Early Warning Signals

  • Tissue-Specific Biomarkers

    Click Image To Enlarge +
    Almac Diagnostics has developed a microarray technology that it says is optimized to work with FFPE tissue.

    A presentation given by Richard Kennedy, M.D., Ph.D., vp of experimental medicine at Almac Diagnostics, focused on the use of customized microarray-analyzed fresh frozen paraffin-embedded (FFPE) cancer tissue biopsies to identify novel cancer biomarkers. “We’ve developed a microarray technology that is optimized to work with FFPE tissue,” he said. “Most clinical trial datasets include large FFPE databases, and we are now able to analyze these in great detail using our technology.”

    Almac developed disease-specific array (DSA) technology for five major cancers (colon, breast, lung, prostate, and ovarian). It has used the technology to develop a pipeline of diagnostic tests, one of which—a test for stage 2 colon cancer—was discussed in great detail by Dr. Kennedy.

    The goal of the test, which is expected to be submitted to the FDA next year, is to predict which patients are at risk of recurrence following surgery and may benefit from adjuvant chemotherapy. “Typically arrays only work with the fresh [nonfixed or nonpreserved] tissue like frozen or fresh extracted tissue, so these tests are only possible because we’ve been able to use archived tissue samples,” Dr. Kennedy explained.

    To build DSA, Almac sequenced all five cancer transcriptomes and then designed appropriate probe sets on an Affymetrix array format. One special feature of DSA that enables analysis of FFPE tissue samples is that the probes used to detect the message are designed to the true 3´ end of the sample RNA transcripts. This region is amplified better than the 5´ end from archived tissue, Dr. Kennedy said.

    Christopher S. Foster, M.D., Ph.D., D.Sc., George Holt professor of pathology at University of Liverpool, planned to discuss his biomarker research at the meeting. A major premise of his work is that “approximately two-thirds of the prostate cancers do not need urgent treatment at the time of diagnosis because they will progress slowly, whereas one-third of prostate cancers progress relatively quickly.”

    By focusing on developing biomarkers of prostate cancer progression in order to begin phenotyping prostate cancers, Dr. Foster’s research has yielded a number of predictive biomarkers that have been published in peer-reviewed scientific literature. The most powerful of these predictive biomarkers is heat shock protein 2, which enables researchers to accurately segregate between slow-progressing and fast-progressing prostate cancers at the time of diagnosis.

    Dr. Foster plans to identify tissue biomarkers by analyzing spliced RNA transcript levels in prostate cancer biopsies by microarray instead of the more traditional histochemical approach. “That alone is a major step forward. If one can take a patient’s biopsy, phenotype it, and accurately predict its behavior when left untreated, or to begin suggesting drugs or therapies that might or might not be appropriate biologically, then it will be a major leap forward in cancer management.” 


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