Scientists make important pancreatic cancer discovery

NEW YORK — Scientists at Cold Spring Harbor Laboratory have discovered a key biological mechanism that drives the spread of pancreatic cancer and helps explain why one of the most common forms of the disease is so deadly.

The researchers, in the just-released issue of the journal Cell, describe how working with tiny pancreatic organoids — miniature living models of the pancreas — led to their significant step in understanding DNA sequences that underlie the spread of pancreatic ductal carcinoma.

Cancer of the pancreas has the reputation of being one of the most lethal malignancies because of its overwhelming tendency to metastasize, spreading to sites beyond the gland itself, researchers said.

Pancreatic ductal cancer, a widely diagnosed form of the disease, often is called a “silent killer” because it produces no overt symptoms in its early development.

There is no method of routine screening to detect the malignancy in its earliest evolution. By the time most pancreatic ductal cancers are found, the disease already has spread elsewhere in the body.

Cold Spring Harbor Laboratory scientists in the lab of Dr. David Tuveson, director of cancer therapeutics, unmasked one of the cancer’s longest-held secrets: Pancreatic cancer spreads because metastatic cells carry short sequences of DNA, called enhancers, that drive the cancer’s spread.

These DNA enhancers are not evident in “primary” pancreatic tumor cells, which make up the cancer in its earliest stages of evolution.

These enhancers, the scientists found, actively direct the cancer’s spread beyond the pancreas.

“We show that to metastasize, the cell has to change. In effect, its whole telecommunications network — its enhancers — are being reprogrammed,” Dr. Christopher Vakoc, a co-author of the study, said in a statement.

The team was able to decipher the role that the enhancers play by developing organoids that were both replicas of primary tumor cells and replicas of metastatic ones — those that possess the wanderlust to travel to distant sites, he said.

In the laboratory, organoids are small, glistening spheres, whether primary or metastatic. Each pint-size organoid is about the size of the period at the end of a sentence.

The miniature models allow researchers to understand why the cancer forms in the first place and how it receives genetic messages to spread.

Tuveson also is director of research for The Lustgarten Foundation, the nation’s largest private supporter of pancreatic cancer scientific and medical research. He has long said that cancer of the pancreas is one of the most confounding human diseases. Only 7 percent of patients survive five years after diagnosis.

This year, the cancer is expected to be diagnosed in about 53,070 people nationwide — about 27,670 men and 25,400, according to the American Cancer Society.