RNA test might reveal early cancer, offer drug target.

By analyzing snippets of genetic material called microRNAs in the intestinal cells of people with colorectal cancer, researchers have devised a technique that might reveal which cancers are at the highest risk of recurrence. The finding could also open the way for new drugs targeting aberrant microRNAs that contribute to the malignancy.

Certain genes carry the blueprints for microRNAs. The scientists compared the activity pattern of 248 such genes in healthy colon tissue with those in cancerous tissue. The scan revealed 16 of these microRNA genes whose behavior was different in the two tissue categories.

The researchers then studied the fastgrowing cells that line the colon and that are normally sloughed off and replaced every 5 days or so. These cells are generated in pockets embedded in the lining of the colon called crypts, says Bruce Boman, a physician and geneticist at Thomas Jefferson University in Philadelphia.

Stem cells that reside deep within these crypts divide and spin off a regular supply of daughter cells, which then differentiate as needed to replace the colon-lining cells. Boman and his team tested the activity of the 16 microRNAs in cells from deep within these crypts. They found that their test correctly predicted whether cells from these crypts were cancerous or healthy, Boman says.

Scientists are still deciphering the normal job of microRNAs. Research has shown that they influence whether many genes are activated or silenced. "It may be that microRNAs regulate genes that prevent stem cells from dying or [regulate] other genes that keep the stem cells active and proliferating," Boman says.

As such, these microRNAs might influence the size of the stem cell population. "Colorectal cancer may be a disorder of too many stem cells. If stem cell self-renewal requires regulatory mechanisms based on microRNA, then maybe you can target those mechanisms for colorectal cancer treatment," says Boman.

Many colorectal cancer patients have surgery that appears to remove all of their cancer, only to have it crop up again later. The microRNA test might enable scientists to predict which patients have overactive stem cells in their colon lining and thus are at high risk of a cancer recurrence, Boman says.

Moreover, microRNAs "are going to be excellent candidates for targeted therapeutics,' he says. Devising compounds that interfere with the aberrant microRNAs might derail the impetus to spur cancer-stem cell growth.