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Cancer cells revert to normal at specific signal threshold, Stanford researchers find
Date:6/30/2008

STANFORD, Calif. - Cancer starts when key cellular signals run amok, driving uncontrolled cell growth. But scientists at the Stanford University School of Medicine report that lowering levels of one cancer signal under a specific threshold reverses this process in mice, returning tumor cells to their normal, healthy state. The finding could help target cancer chemotherapy to tumors while minimizing side effects for the body's healthy cells.

The researchers identified a precise threshold level of the signaling molecule Myc that determined the fate of tumor cells in a cancer of the immune system in mice. Above the threshold, high levels of Myc drove immune cells to grow too large and multiply uncontrollably. When the researchers lowered Myc levels below the threshold, the same cells shrank to normal size, stopped multiplying and began dying normally.

"This is a new concept," said Catherine Shachaf, PhD, an instructor in microbiology and immunology who shared lead authorship of the study with colleague Andrew Gentles, PhD, a research associate in radiology. Previous research demonstrated that turning Myc and other cancer signals all the way off can kill a tumor, but this is the first time scientists have demonstrated a specific midway point at which a cancer signal reverted to a healthy level, Shachaf said. The findings will be published in the July 1 issue of Cancer Research.

Identifying the threshold was important because Myc functions in both healthy and cancerous cells as a transcription factor, a protein signal that binds DNA to turn genes on or off. Excess Myc contributes to about 50 percent of human cancers, including malignancies of the immune system and lung.

But Myc is essential, at lower levels, for normal cell function. So, switching Myc all the way off is not an option for treating cancer.

"I wanted to figure out, if we had a drug to turn off Myc, how could we give it to people without hurting them
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Contact: Erin Digitale
digitale@stanford.edu
650-724-9175
Stanford University Medical Center
Source:Eurekalert

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