Scientists have identified a potential drug that may be able to knock out a wide variety of cancer cells while leaving healthy cells unscathed. If it works in human trials already under way, the drug would be a significant advance over current chemotherapy agents and may someday help patients who do not respond to other drugs.
Flavopiridol, like many other drugs, acts by blocking proteins essential for cell division. It has been in clinical trials for kidney, prostate, colon, and other cancers since 1998. Last year, a new talent came to light: Flavopiridol also blocks a protein that helps transcribe DNA into messenger RNA (mRNA), the first step in producing a protein from a gene and a process that all cells need to stay alive. Cancer researcher Louis Staudt of the National Cancer Institute in Bethesda, Maryland, and his colleagues was curious about the effect of flavopiridol on B-cell lymphoma.
When Staudt tested how many genes flavopiridol inhibited, he was surprised to find that it turned off transcription in a multitude. Yet rather than kill all kinds of cells, flavopiridol targeted cancerous ones. Puzzled, Staudt decided to measure how long the mRNA of each of 5000 genes lasts after treatment with flavopiridol. In the 13 September issue of Genome Biology, Staudt's team reports that mRNA durability relates to gene function. Genes known to participate in cell death or cell division, two processes that, when gone awry, contribute to cancer, often had short-lived mRNA. Once flavopiridol hit the cell, genes with short-lived mRNA couldn't make more of it and the mRNA quickly degraded.
"It has a general effect on transcription, and the patients are not keeling over," said cancer researcher John Reed of the Burnham Institute in La Jolla, California. "That's pretty amazing." The drug is being tested in small groups of patients (though none with B-cell lymphoma), but Reed cautions that it's difficult to predict how successfully the drug will combat cancer.
Related sites
Research paper
in Genome Biology
More
about how flavopiridol works, from the Journal of Biological
Chemistry
Staudt lab Web
site
Reed lab
Web site
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