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April 15, 2011 (Vol. 31, No. 8)

Robust Multimodal Approach Essential to Conquer Cancer

Quest for a Single Biomarker to Measure or Detect the Presence of Disease Must Cease and Desist

  • A Plethora of Proteins

    It is the complex interplay of normal and cancerous cells that defines future research into biomarkers for cancer progression. The search for a single biomarker to measure or even detect the presence of cancer is over.

    Clinical approaches haven’t yet caught up, though. Diagnosis and measurement of progression use a multimodal approach, modes which are generally limited to imaging, biopsy, and a few biomarkers. More robust measurements, especially noninvasive types integrating data from several biomarkers, are trickling onto the market.

    In late 2009, the FDA approved OVA1 (Vermillion and Quest Diagnostics), a five-protein serum assay for ovarian tumor malignancy. Genetic tests for risk factors have become more commonplace, and fluorescence in situ hybridization (FISH) tests exist for tumors to determine mutations and thus treatment susceptibility.

    The ultimate biomarker-based assay for cancer diagnosis and progression would not only measure circulating tumor cells (as existing product CellSearch, from Veridex and Quest Diagnostics, does) but also check the composition of those tumor cells; certain mutations turn circulating tumor cells into cells with complete capabilities for founding new tumors elsewhere.

    Cancer is also an opportunistic disease. Indicator compounds such as abnormal protein levels and metabolites are important but so are indicators of normal function. By connecting large pools of data (as microarray and other multiplex assays become cheaper and easier), a fuller, more individualized picture of cancer pathology can be generated, and treatments can be appropriately tuned.

    A treatment that shrinks a tumor but fails to kill its stem cell population will lead to eventual recurrence but may still be useful in making those cancer stem cells more vulnerable to other agents. If your test shows that those stem cells are still alive (or worse, circulating), then different treatments can be applied.

    In essence, the rise of highly multiplexed assays makes single biomarker tests outdated, and makes less-specific/less-sensitive biomarkers more useful as part of a portfolio to account for the myriad ways in which cancer can manifest itself in the body. A 2008 study in Clinical Cancer Research described how measuring six proteins could provide an ovarian cancer assay with 95% sensitivity and 99% specificity, versus 72% sensitivity and 95% specificity for one protein alone.

    By improving sensitivity, the fraction of false negatives decreases; by increasing specificity, the fraction of unnecessary biopsies falls as well. It is time for us to use all of our molecular tools side-by-side in diagnosing and measuring the progression of cancer.

Posted 7/20/2011 by Peter Nowack

Ladies and Gentlemen,   I have to apologize for commenting now in late July when the contribution goes back to April.   Therefore I will make a short comment: I am wondering whether PCA3 should not be brought into the picture. Would that not change the percentage of subsequent biopsies producing negative results?   Sincerely, Peter Nowack


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