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New cancer drug screening technique more closely mirrors reality
Date:3/14/2010

ntage of these signals to fuel their own growth."

Evidence from a variety of studies suggests that these otherwise normal elements of the tumor microenvironment can impede the effectiveness of anti-cancer drugs and allow cancer to become resistant to different therapies one of the biggest challenges in oncology.

To get a better understanding of this phenomenon and develop treatments to address it, Mitsiades and his colleagues developed a technique in which tumor and normal cells are "co-cultured" that is, grown together and exposed to hundreds or thousands of compounds in large-scale screening tests. In the technique, dubbed "cell-specific in vitro bioluminescence imaging," or CS-BLI, the cancer cells in each sample are equipped with a gene that makes them glow a process unaffected by the normal cells nearby. By measuring the amount of light emitted by each sample after treatment, investigators can determine which compounds are most proficient at killing tumor cells, and whether this effectiveness changes when normal cells are around the tumor. (To make sure the candidate drugs aren't also killing normal cells, researchers can do a "counter-screen," in which they measure the effect of each compound on the normal cells.)

While there are other techniques for screening drug activity in co-cultures of malignant and normal cells, they either involve radioactivity or entail a time-consuming process of data capture and analysis, rendering them too cumbersome for large-scale studies, Mitsiades remarks.

With CS-BLI, Mitsiades and his colleagues have identified numerous compounds that acted powerfully against isolated samples of tumor cells but were significantly less effective against the same types of tumor cells co-cultured with non-malignant cells. Perhaps surprisingly, they also identified some compounds which are more effective against tumor cells mixed with non-malignant cells than against tumor cells alone.

In this latter category, res
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Contact: Teresa Herbert
teresa_herbert@dfci.harvard.edu
617-632-4090
Dana-Farber Cancer Institute
Source:Eurekalert

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