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Pancreatic cancer is a surprisingly slow killer

Studies into the genetic changes that occur in pancreatic cancers show the notoriously deadly disease develops over a longer time than thought, and suggest potential new targets for treatments, according to two reports.
/ Source: Reuters

Pancreatic cancer grows slowly, taking years and even decades to develop, a finding that offers the chance to catch it early and cure it, researchers reported on Wednesday.

They said their findings confirm that one of the most lethal cancers kills not because it spreads like wildfire, but because it does not cause symptoms until it is advanced.

"That provides a large window of opportunity to try to detect the presence of these cancers in the first 20 years of their existence, before they become lethal," said Dr. Bert Vogelstein of Johns Hopkins University in Baltimore, who helped lead the study.

"If one can do that, one can in principle cure them by surgery," Vogelstein added in a telephone interview.

Pancreatic cancer is one of the deadliest cancers, killing 95 percent or more of its victims within five years of diagnosis. The American Cancer Society says 42,000 Americans were diagnosed with pancreatic cancer in 2009 and more than 35,000 died of it.

Vogelstein's team, working with British researchers at the Wellcome Trust Sanger Institute and the University of Cambridge, did a kind of genetic archeological dig into pancreatic tumors.

They collected tissue samples during autopsies immediately after patients died from pancreatic cancer, as well as from three patients whose tumors were surgically removed in an attempt to save their lives.

In two papers in the journal Nature, they described how they used mutations in the tumors as a "molecular clock" to time the evolution of the tumors.

DNA mutates at a rate that can be calculated and the researchers already knew which mutations were caused by pancreatic cancer. They compared the DNA mutations in the primary tumor — the first tumor that grew in the pancreas — to the secondary tumors in the liver and other organs.

Family tree of cancer
"We could kind of create a family tree with each successive generation having additional mutations to the genes that started the process," Vogelstein said.

"From doing that it was obvious that it took a very long time, in fact decades, for the cancer to develop to its fully malignant state. That means ... these cancers, at least most of them, do not develop quickly but in fact more like other cancers, including colon cancer."

They estimated it takes an average of 11.7 years before the first true cancer cell develops within a precancerous lesion. It takes another 6.8 years for a tumor to grow and the first cancer cell to break off to go somewhere else in the body, and then 2.7 years until the patient dies.

The hard part is going to be screening for pancreatic cancer. Colon cancer can be found and prevented with colonoscopies, which involve threading a camera through the colon and removing pre-cancerous lesions when they are spotted.

But the pancreas is not easy to get to and even if a tumor can be spotted before it gets too big, it requires complicated surgery to get it out, Vogelstein said.

"The bowel you can just go in and snip it out, which is great," he said.

His team is working on ways to find mutated DNA from pancreatic tumors or pre-cancerous lesions in the blood. Other teams are looking for ways to find circulating tumor cells, while other groups may look at using MRI or CT scans to detect the tumors before they cause symptoms.