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Genomes on 'chips' boon to cancer research

BioMed Central

New research published in Genome Biology uses microchips coated with DNA to discover the surprising way that the drug flavopiridol acts to kill cancer cells. This research, carried out in a collaboration between the National Institutes of Health, the National Cancer Institute and the EMMES Corporation, is an example of the exciting new ways in which genomic research techniques are now being applied to medicine.

The study shows that, contrary to the expectation of those who first used the drug successfully, flavopiridol works by broadly inhibiting messenger RNA (mRNA) molecules, which are responsible for carrying the information (encoded by DNA) to cellular protein factories (called ribosomes). The inhibition of mRNA ultimately leads to a halt in the production of certain proteins as the mRNA molecules circulating around the cell are degraded without being replaced.

This posed an interesting question to the researchers - If flavopiridol works in such a general way, how does it manage to kill cancer cells in preference to normal cells?

The answer lies in the differences between normal and cancerous cells, which Staudt and collegues analysed using DNA coated microchips known as microarrays. It seems that the RNA molecules responsible for relaying the message that instructs a cancer cell to grow uncontrollably are short-lived. Cancer cells, therefore rely on constant synthesis of messenger RNA to grow in a cancerous way.

When flavopiridol is present, no new mRNA can be synthesised and so the message to become a cancer cell is not relayed to the ribosomes. Long-lived mRNA molecules do persist despite the inhibition of new mRNA production by flavopiridol, allowing normal cellular processes to continue.

The researchers hope that the identification of short-lived mRNA molecules unique to cancer cells could help to identify the types of cancer that would respond to treatment with flavopiridol.

To read the full text of this article visit: http://genomebiology.com/2001/2/10/research/0041/

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