CSH’s David Tuveson works to cure pancreatic cancer

CSH’s David Tuveson works to cure pancreatic cancer

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Not only treatment, but early diagnosis is a challenge in dealing with this tumor

It’s an all-too-familiar pattern. Someone he’s never met reaches out to David Tuveson for his opinion. After exchanging emails or talking on the phone, Tuveson gets an update from a friend or family member: they buried the person who sought his help. He or she died from pancreatic cancer.

“It’s gut-wrenching,” he declared.

A scientist and doctor at Cold Spring Harbor Lab, Tuveson is leading a team of researchers to tackle pancreatic cancer, the most lethal form of cancer.

A world-renowned expert in pancreatic cancer, Tuveson recently opened the Lustgarten Foundation Pancreatic Research Laboratory, where he will direct research on ways to improve medical knowledge of a cancer that kills 250,000 people worldwide each year, including 37,000 Americans.

While that number is smaller than lung cancer, it also carries a more daunting prognosis. Using current treatments, only 6 percent of people with pancreatic cancer survive five years after their diagnosis.

The pancreas is an organ below the stomach that produces hormones including insulin and makes digestive enzymes.

Pancreatic cancer presents several challenges. For starters, it’s difficult to diagnose. The symptoms, which can include abdominal pain, diarrhea, jaundice or weight loss, often appear at a point when the cancer has already progressed.

Scientists at the lab are looking for ways to spot the presence of pancreatic cancer early through blood or urine samples, in much the same way doctors check for cholesterol levels, blood sugar and blood pressure to look for signs of heart diseases.
Pancreatic tumors themselves are also difficult to penetrate.

“The tumor is hard, like a rock,” explained Tuveson. “Other tumors are soft, like a grape.”
Pancreatic tumors have a type of cement between the cancer cells called stroma. That makes it difficult for vessels to pump blood. Even the most effective medicine would need some way to loosen the stroma to deliver targeted tumor toxins. Tuveson and others have shown that drug delivery is limited in pancreatic cancer.

Indeed, one recent study tested the hypothesis that drugs aren’t getting into the tumor.
This was “the first clinical evidence” in an early-phase trial that drugs aren’t reaching their targets, Tuveson offered. The study should be completed within a year. “This is giving us hope that the science we’re doing is correct. Now, there are a variety of ways to increase the delivery of our therapy.”

Tuveson and his colleagues are looking for ways to develop new drugs.

“We are taking novel platforms and novel payloads that can bind to and inactivate the root causes of cancer,” Tuveson explained.

He is inspired by the opportunity to work with people throughout Cold Spring Harbor, including professors Gregory Hannon, who has done innovative work with RNA, the cousin to DNA, and Adrian Krainer, who has worked with antisense therapies.

Asked to compare the task of diagnosing and treating pancreatic cancer to climbing a mountain, Tuveson suggested that researchers don’t know how far or high they have to climb to understand and conquer this cancer.

“We are scaling this mountain, but no one has ever climbed it,” he suggested.

Tuveson recognizes it’s likely to be a steep ascent.

“Some would say what we’re attempting is not possible,” he said. Many have tried and failed to solve pancreatic cancer, he explained. Tuveson, however, said he ignores the naysayers and feels fortunate for the support of Cold Spring Harbor and the Lustgarten Foundation.

He is inspired by the resources, the energy, and the talent in a lab that includes postdoctoral students, Ph.D.s, and technical staff. If these approaches are effective, they might help in treating other forms of cancer.

Tuveson, who lives on the Cold Spring Harbor campus with his wife Michelle, explained that his early training in medicine prepared him for the interactions with patients and their families when they face the daunting challenge of a pancreatic cancer diagnosis.

“When I was training as a physician in East Baltimore in the late 1980s, a lot of my patients were dying from this new disease no one knew much about, which became known as HIV,” he recalled. “When that happened, I convinced myself I would be an HIV doctor.”

By the time he started his residency in Boston, medicine had come up with treatments for HIV.

“When I went through that very young, I became interested in being a healer,” he said. “I learned how to talk to the families of patients. I became a doctor for the family, equally or more so, than a doctor for the patient.”

As for his pancreatic cancer team, he said he is eager to make progress in understanding and conquering this lethal form of cancer.

“I am the most excited I’ve been in my career,” he explained.