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LI researchers create drug combo to treat pancreatic cancer

Dr. Iok In Christine Chio, a postdoctoral researcher,

Dr. Iok In Christine Chio, a postdoctoral researcher, is seen in Tuveson lab at Cold Spring Harbor Laboratory in Cold Spring Harbor on Thursday, July 28, 2016. Credit: Ed Betz

Medical investigators at Cold Spring Harbor Laboratory have developed promising new insight into the basic biology of pancreatic cancer and have produced a novel drug strategy based on their findings, which they hope to soon test in a clinical trial.

Cancer of the pancreas is notorious for its vague early symptoms and high death rate, two factors that render it a conundrum compared with other malignancies. No statistic involving the disease is more glaring — and grim — than the one that underlies survival: Fewer than 5 percent of patients are alive five years after diagnosis, doctors say

But Iok In Christine Chio, an investigator in the laboratory of Dr. David Tuveson, has homed in on the molecular underpinnings of pancreatic cancer. There she found one of nature’s long-held secrets: Pancreatic cancer cells are veritable storehouses of antioxidants, the kind produced by cells themselves in the bustling thermodynamics that are fundamental to life.

At the core of this chemistry are the free radicals — oxygen molecules that are missing an electron — that are quelled by antioxidants. It’s just that in pancreatic cancer the antioxidants, normally considered the “good guys,” lie at the core of driving the disease, Chio said.

“These are products of the cell and they are important in homeostasis,” said Chio, referring to the basic stability — the equilibrium — usually provided by antioxidants in healthy tissues.

But these compounds play a subversive role in pancreatic cancer typifying the early development of the disease and the overproduction that continues long after tumor cells have matured.

Yet having a full understanding of what had gone awry, the next step, Chio said, was to find a fix. And therein lies the therapy that Chio, Tuveson and the other team members produced.

“We came upon this therapeutic strategy that would hurt the cancer cells but not the normal ones, Chio said.

The team developed a drug strategy that delivers a one-two punch because a cocktail of two medications are involved.

Tuveson said in a statement Thursday that the strategy unveiled the molecular “henchmen” that are at the heart of the cancer.

This finding is not the first advance from Tuveson’s lab that furthered the understanding of a malignancy that will be diagnosed in an estimated 53,070 people nationwide, about 27,670 men and 25,400 women this year, according to the American Cancer Society.

Last year, he announced the successful development of so-called pancreatic organoids, minuscule three-dimensional models of the human gland. The scientists coaxed along the development of these glistening spheres using human pancreatic stem cells as their key ingredient.

Chio said organoids were studied in her research, which uncovered the underlying chemical dynamics of pancreatic cancer.

Dr. Tony Philip, an assistant professor at Hofstra-Northwell School of Medicine and a specialist in cancers of the gastrointestinal tract, said research into treatment strategies for pancreatic cancer are important because there are paltry few drugs available to address the disease.

“Malignant melanoma was once analogous but because of immunotherapies,” he said of medications that recruit the immune system to fight the cancer, the situation has changed dramatically. “Pancreatic cancer has not followed the same storyline,” Philip said. Former president Jimmy Carter was treated with an immunotherapeutic for malignant melanoma that spread to his brain.

Not only are just a handful of drugs routinely used in the treatment of pancreatic cancer, drug resistance often quickly develops making the disease even tougher to fight, Philip said.

He added that pancreatic tumors have a tough scar tissue-like “wall” around them that is difficult for medications to permeate.

Chio and Tuveson, meanwhile, are in the process of planning a clinical trial to test their treatment strategy in patients with the disease.