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Jun 15, 2009 (Vol. 29, No. 12)

Catching Up to Multiplexing Technology

Getting Regulations up to Speed and Clinicians on Board Will Be Key

  • Chemopreventive Resistance

    Click Image To Enlarge +
    miRNAs are increasingly popular targets of multiplexed screening assays for biomarkers.
    (University of Pennsylvania)

    As indicated earlier, miRNAs and multiplexing figure prominently in cancer research. “I’m currently working on colon and pancreatic cancer, trying to link miRNA induction or reduction as a way of determining whether or not cancerous cells would exhibit resistance to chemopreventive agents,” commented Jennie L. Williams, Ph.D., cancer prevention laboratory, State University of New York at Stony Brook, at CHI’s miRNA meeting.

    Dr. Williams uses Marligen’s Vantage™ microRNA Detection Kit, which profiles the expression levels of multiple miRNAs from many different sample types including total RNA, enriched low molecular weight RNA, and degraded RNA. The assays are configured on the Luminex xMAP® bead array allowing for the detection of multiple miRNAs in one sample. In addition, the 96-well format allows many samples to be analyzed in one run.

    Dr. Williams is using this technology on a project in which her group, using derivatives of nonsteroidal anti-inflammatory drugs (NSAIDs), promising colon cancer chemopreventive agents, has demonstrated that treatment with these agents inhibits colon cancer cell growth by inhibiting cell proliferation and enhancing cell killing.

    “However, very little is known about the molecular targets within the cancer cell that are responsible for this effect,” explained Dr. Williams. “microRNAs are known to control gene expression and translational repression or degradation via specific sites at the 3´-UTR of its target mRNAs.” She added that the deletion or mutation of one particular miRNA could potentially lead to the progression of disease.

    Consequently, using total RNA isolated from colorectal cancer cells treated with an NSAID derivative, miRNA distribution patterns were determined and analyzed by Marligen’s multiplex bead arrays. 

    “The clinical response to chemopreventive agents often differs between individuals,” adds Dr. Williams. “Since chemopreventive agents exert their effect through a molecular target, and because these targets are dysregulated in most cancers, it is conceivable to suggest that chemo-resistance occurs due to irregularity at the genetic level.”

    Consequently, the generation and evaluation of chemopreventive agents that address the issue of chemo-resistance is essential. Thus, a correlation of altered levels of miRNA and the expression and/or activation of its target genes may ascertain its association with poor clinical outcome.

    “A number of innovations for treating cancers are becoming available,” Dr. Williams said. “Using multiplexing systems specifically evaluating transcriptional factors that are up- or downregulated in response to treatment with chemopreventive agents pulls it all together.”

    “It’s powerful technology, but this is just another tool in the toolbox,” concluded Dr. Baldwin. “Plenty of doctors want to try something new. But conservatism is there, appropriately, and you need validation. There are also cost implications. A lot of technologies are expensive, and you need to show value and return on your investment of healthcare dollars. More knowledge is good, multiplexed knowledge is better.”


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