More Than Bit Players: Snippets of RNA might sway pancreatic cancer

Cancer of the pancreas is one of the most discouraging diagnoses that a person can receive. The cancer is difficult to detect, so many patients are diagnosed too late for surgical treatment. The majority die within a year of getting the bad news, and only 5 percent survive for 5 years.

Researchers now find that small pieces of genetic material called microRNAs might provide a preview of a tumor’s aggressiveness and offer targets for combating the disease.

While the majority of genes supply blueprints for protein assembly, a few hundred contain the instructions for making microRNAs. Within cells, these molecules switch genes on or off.

The purpose of this regulatory function is still poorly understood. However, several studies have linked microRNAs to cancer (SN: 4/22/06, p. 254: Available to subscribers at RNA test might reveal early cancer, offer drug target; 6/11/05, p. 371: Cancer Link: MicroRNA grabs the spotlight).

In the new research, scientists analyzed the microRNA profile of pancreatic tissue of three kinds: normal, inflamed by pancreatitis, and cancerous. The tissue samples had been obtained from 65 patients who, years earlier, had had biopsies followed by surgery to remove pancreatic cancer. Despite treatment, the patients had survived only 15.5 months, on average, after being diagnosed.

The researchers gauged the activity patterns of dozens of genes known to encode microRNAs to see whether any were especially busy or idle in the tumor tissue. Ten were active in cancerous cells but not in either of the benign cell types, the researchers report in the May 2 Journal of the American Medical Association. Two of these—miR-21 and miR-155—had been previously implicated in other cancers, says study coauthor Mark Bloomston, a surgical oncologist at Ohio State University in Columbus.

Bloomston and his colleagues then cross-checked the activity of the microRNA genes against each patient’s survival time. Patients whose tumor cells had an active gene for the microRNA called miR-196a-2 tended to succumb particularly rapidly.

Bloomston cautions that the new findings are only associations, not proof of cause and effect. “But this early data gives us some targets to start looking at,” he says.

To diagnose the disease, doctors might eventually test for telltale microRNA profiles in individuals at elevated risk. Pancreatic cancer risk has been tied to smoking, pancreatitis, and a family history of the cancer.

The survival data in the new study hint that microRNAs might also shed light on a patient’s prognosis, says clinical pharmacologist Scott Waldman of Thomas Jefferson University in Philadelphia. A different treatment strategy might be recommended when a doctor knows that a patient has an aggressive form of cancer, he says.

Scientists studying microRNAs “have uncovered a previously unanticipated level of regulation … in the machinery inside a cell,” says Waldman.

The best outcome of microRNA research might be in therapeutics. If some microRNAs can be shown to promote cancer, “then drugs or other agents might disrupt these molecular mechanisms,” Waldman says. “Particularly in pancreatic cancer, anything added to the armamentarium that allows us to intervene is welcome.”

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