A dense enclosure of tissue surrounding pancreatic tumors has long made the cancer difficult to treat, but a team of scientists at Cold Spring Harbor Laboratory has unraveled the mystery of the inviolable barrier, possibly opening a new door for therapy.
Pancreatic cancer arguably has one of the worst outcomes among all forms of cancer with a one-year relative survival rate of 20 percent and a five-year rate of 7 percent, according to the American Cancer Society.
Dr. Abram Handly-Santana, a researcher who specializes in pancreatic cancer at Cold Spring Harbor Lab, attributes much of the cancer’s poor survival rate to the structural makeup of the tumor’s outer shell. This enclosure, known as a stroma, might as well be armor because its presence has made it nearly impossible for cancer-killing drugs to penetrate, Handly-Santana said.
“The stroma in pancreatic cancer has always been a poignant target for researchers because it has made treatment very difficult,” Handly-Santana said, noting that the deadly barrier has long proved an enigma for both doctors who treat patients and scientists who study the cancer’s biology.
The wall is so tough, Handly-Santana added, that some cancer clinical trials involving experimental medications designed to breach the barrier, had to be abandoned midstream. The drugs were so harsh they further sickened already ailing patients, he said.
What had not been well known until now were all of the basic building blocks making up the wall, something that Handly-Santana and his collaborators have delineated and defined. In so doing they have found a possible new target — a doorway through the stroma — to reach the cancer. That vulnerability, he said, is made up of fibroblast cells, a main contributor to the stroma.
“The stroma is not as well understood as many researchers thought it was. So we are trying to enlighten the field, and the better we understand it, the better we can target it in the future,” Handly-Santana said.
He and Giulia Biffi, Daniel Ohlund and 18 other Cold Spring Harbor Laboratory scientists helped make the discovery and reported their results in the current issue of the Journal of Experimental Medicine. They used tiny 3D organoids, miniature balloon-like structures in a sea of gelatinous goo to zero in on stroma’s structure.
Dr. Craig Devoe, acting chief of hematology and oncology at Northwell Health’s Monter Cancer Center in New Hyde Park, said the stroma has long been known as an inhibitor to drug penetration in pancreatic cancer.
The structure not only blocks the uptake of medication but also increases pressure around the tumor, Devoe said.
He added that the puzzle of pancreatic cancer has been difficult to solve because there are so many biological factors that contribute to the cancer’s growth and proliferation.
“The other thing is that the tumor itself is resistant to various chemotherapies,” Devoe said, underscoring that when tumors repel medications, it becomes increasingly difficult to treat the patient.
“The biggest issue is that pancreas cancer has a high metastatic potential,” Devoe said, which means tumors can spread very early in their evolution. Even when the cancer appears to be very small on a scan, he said, “it is very possible that it has already metastasized.”
Symptoms are sometimes vague but can include jaundice as well as persistent gastrointestinal and mid-back pain.
The cancer tends to run in families, he said, noting that several members of former President Jimmy Carter’s family died of the disease.
Although Carter did not have pancreatic cancer, he was successfully treated for malignant melanoma that spread to the brain. Devoe said the p16 gene is implicated in both pancreatic cancer and melanoma and tends to run in families.