Pancreatic cancer: Slow and deadly

JOHNS HOPKINS (US) — Pancreatic cancer develops and spreads much more slowly than scientists have thought, new research finds.

“For the first time, we have a quantifiable estimate of the development of pancreatic cancer, and when it would be best to intervene,” says Christine Iacobuzio-Donahue, associate professor of pathology and oncology at Johns Hopkins University, “so there is potentially a very broad window for screening.”

The problem, she adds, is that right now “pretty much everybody is diagnosed after that window has closed.”

Pancreatic cancer is notoriously difficult to detect in its early stages because there are frequently few symptoms. Current imaging techniques are not specific for cancer.

The new study shows that “many pancreatic cancer cases have a long lag time before they are detected through conventional tests. This leaves room to develop new early, diagnostic tools and intervene with potentially curative surgery,” says Bert Vogelstein, professor and director of the Ludwig Center for Cancer Genetics and Therapeutics and an investigator at the Howard Hughes Medical Institute.

The research, published in the Oct. 28 issue of the journal Nature, suggests that it takes at least a decade for the first mutation in a pancreatic lesion to turn a cell into a full-fledged cancer cell.

After the first cancer cell appears, it takes an average of nearly seven more years for that cell to turn into the billions that make up a cancerous tumor the size of a plum, after which at least one of the cells within the tumor has the ability to spread to other organs. Patients die an average of two and a half years after this metastasis.

The results contradict the idea that pancreatic cancers metastasize very early in their development, Iacobuzio-Donahue says.

For the study, scientists collected tissue samples during autopsies of seven patients who died from pancreatic cancer that had metastasized to other organs. Because the tissue samples were taken within six hours of each patient’s death, the scientists were able to keep some of the cells alive long enough to extract the DNA and sequence the series of chemical “letters” that form genes.

In each patient, metastatic deposits were found in two or more sites in the body, most often the liver, lung, and lining of the abdomen. The researchers found similar mutations present in both the areas of metastasis and in the primary pancreatic tumors from which the metastases arose.

They also identified and classified the types of mutations, ones that occur before metastasis and others that happen after the cancer has spread. Both types of mutations were present within the primary tumor years before the metastases became clinically evident, Iacobuzio-Donahue says.

Using mathematical models to study the timing of pancreatic cancer progression, the scientists conservatively estimated an average of 11.7 years before the first cancer cell develops within a high-grade pancreatic lesion, then an average of 6.8 years as the cancer grows and at least one cell has the potential to spread, and finally, an average of 2.7 years from then until a patient’s death.

The scientists say the goal is develop a pancreatic cancer screening method similar to the protocol used for breast and colon cancer. Though early stages of pancreatic cancer cause no symptoms, Iacobuzio-Donahue says, perhaps at a certain age people should undergo an endoscopy to screen for pancreatic cancer.

Endoscopy is a procedure allowing doctors to look inside the body through the use of an instrument that has a tiny camera attached to a long, thin tube.

The genome sequencing work received support from many organizations, including the National Institutes of Health and the Bill and Melinda Gates Foundation.

Other scientists involved in the research were from Johns Hopkins, Harvard University, and the University of Edinburgh.

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