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Honing in on Potential Cancer Drugs

By Kate Ruder

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Leukemia and Lymphoma
Microarrays

Myriad chemicals sitting in laboratories at pharmaceutical companies and universities have the potential to become cancer drugs if only scientists could figure out which ones work.

Researchers in Boston have developed a technique for identifying chemicals that affect cancer cells by altering the way genes are “turned on” and “turned off” in the cell. In the process, they believe they have developed a new, useful technology for screening potential drugs by looking at their effect on the genetic signatures of tumor cells.

The research does not provide a breakthrough for any particular type of cancer. Instead, the long-term goal is to be able to use the technique to screen thousands of drugs that work on different types of tumors.

In a new study, they tested the technique in leukemia cells and used genetic signatures to identify chemicals that help leukemia cells mature into cells that behave like normal white blood cells.

The cells in this type of leukemia, called acute myelogenous leukemia, never mature into healthy white blood cells that are part of the immune system. It is the most common type of leukemia diagnosed in adults.

Todd Golub at the Dana-Farber Cancer Institute in Boston, Massachusetts, led the research on what is called gene expression-based high-throughput screening, or GE-HTS for short.

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Golub and his colleagues screened 1,700 chemicals and correctly identified eight of these that trigger changes in a cell’s gene activity. Then they confirmed that the chemicals were in fact helping the leukemia cells mature into cells that behave normally.

They used a group of FDA-approved drugs with known mechanisms of action to give them good clues to what they were seeing when they tested the drugs inside cells.

Eventually they hope to use this screening method to study other drugs and to further evaluate the compounds in this study before testing them in animals and humans.

Stegmaier, K. et al. Gene expression-based high-throughput screening (GE-HTS) and application to leukemia differentiation. Nature Genetics (Published online February 8, 2004).

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