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Dormant Cancer: Lack of a protein sends tumor cells to bed

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2:07pm, October 13, 2004
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One standard approach to curing cancer is to kill off malignant cells, and doctors consider their treatment a success when no cancerous cells remain. However, many patients whose test results show no malignancy have their cancer reappear years later. New research suggests an explanation.

Scientists working with mice find that when they crank up production of a protein called Myc, they spur liver-tumor growth, and stopping Myc manufacture halts it. Although the cancer then regresses, not all the tumor cells die, the researchers find. Some differentiate into what appear to be normal liver cells. But their cancerous proclivity reawakens when the cells are given the right cue—a new jolt of Myc, the researchers report in an upcoming Nature.

A dormant cancer might not be so bad, says study coauthor Dean W. Felsher of Stanford University School of Medicine. "If we can make cancer sleep for a lifetime, maybe that's good enough," he says.

Myc is a much-studied protein because it turns on or off many genes that influence cell replication. Past research suggested that Myc might orchestrate the shadowy changes by which a normal cell becomes malignant.

To test the protein's effects, Felsher and his colleagues genetically engineered mice to make excess Myc in their liver cells. The new genetic trait also shut down Myc production in the presence of a common antibiotic.

The mice grew up healthy when given a steady supply of the antibiotic. But when the drug was withdrawn, all the mice developed aggressive liver cancer during the next 12 weeks or so. Tests revealed high concentrations of Myc in the tumors.

When the mice were again started on the antibiotic, all showed a sharp decrease in Myc and rapid tumor shrinkage.

Further tests revealed that some tumor cells deprived of excess Myc reverted to looking and behaving as normal liver cells do, without signs of aberrant growth.

Scientists haven't known why tumors reappear in many patients who had seemed free of their earlier cancer, says Nelson Fausto of the University of Washington School of Medicine in Seattle. Therefore, the evidence of a dormant malignancy is "an extremely interesting finding," he says.

Because Myc activates a host of genes involved in cell replication, it could be considered "an Achilles' heel of cancer," says Francesco Feo of the University of Sassari in Italy. Scientists are pursuing various strategies for neutralizing Myc, but most are in the early stages of research, he says.

"There's no doubt that [Myc] is a very important target," says David L. Levens of the National Cancer Institute in Bethesda, Md.

But Myc participates in several essential functions, so shutting down its production may be too disruptive to healthy cells. Moreover, Feo cautions that cancer cells often compensate for the loss of a protein.

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