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Pancreatic Cancer

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‘Jeopardy!’ host Alex Trebek, left, pictured with former contestant Kevin Foley of Mount Sinai, has been diagnosed recently with pancreatic cancer. Photo from Alex Foley

By Anthony Frasca

After multiple Emmy award-winning “Jeopardy!” host, Alex Trebek, announced that he had stage 4 pancreatic cancer, the news has drawn attention to the disease and raised questions related to the latest advances in diagnosis and treatment of pancreatic cancer.

Dr. Aaron Sasson, director of the Pancreatic Cancer Center at Stony Brook University and chief of the Surgical Oncology Division, said little has changed when it comes to a doctor’s ability to diagnose the cancer any earlier.

“But we have made improvements in imaging of pancreatic cancer,” he said. “That is, the quality of CT scans and MRIs has improved over the years.”

Kerri Kaplan, president and CEO of the Lustgarten Foundation, said the disease has been “notoriously difficult” to detect and treat. The organization is dedicated to pancreatic cancer research.

“Although great strides are being made to detect pancreatic cancer earlier, this disease has few warning signs and vague symptoms that may range from back pain, fatigue and loss of appetite, amongst others,” she said in an email.

Kaplan added, “Even when there are early signs and symptoms, they may easily be attributed to other illnesses. Because of this, patients are often diagnosed when the cancer is at an advanced stage or has spread to other organs — making them ineligible to undergo surgery, which is the best chance at long-term survival.”

According to the foundation, pancreatic cancer research is moving faster than ever before. The nonprofit is funding a range of innovative projects including artificial intelligence in a partnership with Pancreatic Cancer Collective to use computational approaches to identifying high-risk pancreatic cancer populations, and CancerSEEK, which is an early detection initiative that uses blood testing to identify eight different types of cancer including pancreatic cancer.

Other Lustgarten projects include Dr. David Tuveson of Cold Spring Harbor Laboratory leading a personalized approach to medicine called organoids for personalized therapy — a three-dimensional cell culture system which reproduces a patient’s tumor to test it repeatedly with different drugs. This approach will enable researchers to determine how a pancreatic cancer patient will respond to various treatments. And with an improved imaging and early detection project, scientists from a broad range of disciplines focus on the use of computers to recognize patterns in medical imaging with the goal of finding tumors when they are otherwise undetectable by the human eye.

Also, as a result of Lustgarten-funded research, the U.S. Food & Drug Association recently approved Keytruda as the first immunotherapy treatment for advanced pancreatic cancer patients whose tumors have a unique genetic mutation.

“In the last 10 years our understanding of pancreatic cancer has significantly improved,” Sasson said. “I think we are on the cusp of something remarkable in the next couple of years coming out with regards to treatment. Our understanding of the genetics the biology and immunotherapy of pancreatic cancer, all those things are going to be realized, I’m hopeful, in the next couple of years.”

The five-year survival rate for pancreatic cancer is 9 percent according to the American Cancer Society. Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. Improvements in survival rates for pancreatic cancer are challenging because nearly half of the cancers are not detected until they are in advanced stages.

Photo by Ela Elyada

By Daniel Dunaief

What if, instead of defeating or removing enemy soldiers from the battlefield, a leader could convince them to join the fight, sending them back out to defeat the side they previously supported? That’s the question Giulia Biffi, a postdoctoral researcher at Cold Spring Harbor Laboratory, is asking about a particular type of cells, called fibroblasts, that are involved in pancreatic cancer.

Fibroblasts activated by cancer cells secrete a matrix that surrounds cancer cells and makes up about 90 percent of pancreatic tumors.

Giulia Biffi. Photo by ©Gina Motisi, 2018/CSHL

Responding to a molecule called IL-1, an inflammatory potential tumor-promoting fibroblast may enhance the opportunity for cancer to grow and spread. Another type of fibroblast responds to TGF-beta, which potentially enables them to restrain tumors.

Researchers had suggested that the inflammatory fibroblasts are tumor promoting, while the myofibroblasts are tumor defeating, although at this point, that still hasn’t been confirmed experimentally.

Researchers knew TGF-beta was important in biology, but they didn’t know that it was involved in preventing the activation of an inflammatory tumor-promoting version.

Biffi, however, recently found that IL-1 promotes the formation of inflammatory fibroblasts. She believes these fibroblast promote tumor growth and create an immunosuppressive environment.

In an article published in the journal Cancer Discovery, Biffi showed that it’s “not only possible to delete the population, but it’s also possible to convert [the fibroblasts] into the other type, which could be more beneficial than just getting rid of the tumor-promoting cells,” she said.

Biffi works in Director Dave Tuveson’s CSHL Cancer Center laboratory, which is approaching pancreatic cancer from numerous perspectives.

Her doctoral adviser, Sir Shankar Balasubramanian, the Herchel Smith Professor of Medicinal Chemistry at the University of Cambridge, suggested that the work she did in Tuveson’s lab is an extension of her successful research in England.

“It is evident that [Biffi] is continuing to make penetrating and important advances with a deep and sophisticated approach to research,” Balasubramanian explained in an email. “She is without a doubt a scientist to watch out for in the future.”

To be sure, at this stage, Biffi has performed her studies on a mouse model of the disease and she and others studying fibroblasts and the tumor microenvironment that dictates specific molecular pathways have considerable work to do to extend this research to human treatment.

She doesn’t have similar information from human patients, but the mouse models show that targeting some subsets of fibroblasts impairs cancer growth.

“One of the goals we have is trying to be able to better classify the stroma from pancreatic cancer in humans,” Biffi said. The stroma is mixed in with the cancer cells, all around and in between clusters of cells.

The results with mice, however, suggest that approaching cancer by understanding the molecular signals from fibroblasts could offer a promising additional resource to a future treatment. In a 10-day study of mice using a specific inhibitor involved in the pathway of inflammatory fibroblasts, Biffi saw a reduction in tumor growth.

If Biffi can figure out a way to affect the signals produced by fibroblasts, she might be able to make the stroma and the cancer cells more accessible to drugs. One potential reason other drugs failed in mouse models is that there’s increased collagen, which is a barrier to drug delivery. Drugs that might have failed in earlier clinical efforts could be reevaluated in combination with other treatments, Biffi suggested, adding if scientists can manage to target the inflammatory path, they might mitigate some of this effect.

A native of Bergamo, Italy, which is near Milan, Biffi earned her doctorate at the Cancer Research UK Cambridge Institute. Biffi lives on a Cold Spring Harbor property which is five minutes from the lab.

When she was young, Biffi wanted to be a vet. In high school, she was fascinated by the study of animal behavior and considered Dian Fossey from “Gorillas in the Mist” an inspiration. When she’s not working in the lab, she enjoys the opportunity to see Broadway shows and to hike around a trail on the Cold Spring Harbor campus.

Biffi started working on fibroblasts three years ago in Tuveson’s lab. “I really wanted to understand how fibroblasts become one population or the other when they were starting from the same cell type,” she said. “If they have different functions, I wanted to target them selectively to understand their role in pancreatic cancer to see if one might have a tumor restraining role.”

A postdoctoral researcher for over four years, Biffi is starting to look for the next step in her career and hopes to have her own lab by the end of 2019 or the beginning of 2020.

When she was transitioning from her doctoral to a postdoctoral job, she was looking for someone who shared her idealistic view about curing cancer. Several other researchers in Cambridge suggested that she’d find a welcome research setting in Tuveson’s lab. Tuveson was “popular” among principal investigators in her institute, Biffi said. “I wanted to work on a hard cancer to treat and I wanted to work with [Tuveson].”

Biffi hopes that targeting the inflammatory pro-tumorigenic fibroblasts and reprogramming them to the potentially tumor-restraining population may become a part of a pancreatic cancer treatment.

She remains optimistic that she and others will make a difference. “This can be a frustrating job,” she said. “If you didn’t have hope you can change things, you wouldn’t do it. “I’m optimistic.”

Biffi points to the hard work that led to treatments for the flu and for AIDS. “Years back, both diseases were lethal and now therapeutic advances made them manageable,” she explained in an email. “That is where I want to go with pancreatic cancer.”

Aaron Sasson. Photo courtesy of Stony Brook Medicine

By Daniel Dunaief

Thanks to the efforts of Stony Brook University School of Medicine’s Chief of Surgical Oncology Aaron Sasson and numerous doctors and researchers at Stony Brook, Long Island has its first National Pancreas Foundation Center.

A nonprofit organization, the National Pancreas Foundation goes through an extensive screening process to designate such centers around the country, recognizing those that focus on multidisciplinary treatment of pancreatic cancer. The NPF offers this distinction to those institutions that treat the whole patient and that offer some of the best outcomes and improved quality of life for people suffering with a disease who have an 8 percent survival rate five years after diagnosis.

Sasson appreciates the team effort at the medical school. “As opposed to one person leading this, there are many people here who are required to have an interest in pancreatic cancer,” he said. “We are not only looking to build a great infrastructure for the treatment of pancreatic cancer, but we’re also looking to build a team for research on pancreatic cancer.”

Sasson highlighted the research efforts led by Yusuf Hannun, the director of the Cancer Center at SBU, who has helped attract a “tremendous number of scientists” to engage in research into this disease.

The recognition by the NPF helps the university recruit physicians who are clinically interested in developing ways to improve the outcome for patients.

Pancreatic cancer presents particular challenges complicated by its biological aggressiveness, its difficulty to detect and by the many subtypes of this disease. “It’s similar to lung and breast cancer,” Sasson said. “There are many facets of those cancers. You can’t lump them all together.”

Researchers and clinicians are still trying to understand pancreatic cancer in greater detail. Once they have done that, they can advance to treating the possible subtypes.

Numerous researchers at SBU have developed collaborations with scientists at Cold Spring Harbor Laboratory. David Tuveson, the director of the National Cancer Institute-designated Cancer Center, has engaged in collaborations with SBU scientists in his work on organoids, which are model human organs grown in a lab. Scientists use organoids to test drugs and molecular pathways involved in pancreatic cancer.

Members of the Long Island community can take comfort in the continuing dedication of the numerous staff members committed to finding a cure. “Residents of Suffolk County and Long Island should be proud of what Stony Brook has been able to accomplish,” Sasson said.

Stony Brook University has been involved in several clinical efforts. The university developed a drug called CPI-613, for which Rafael Pharmaceuticals is in the early stage of clinical trials in combination with other drugs.

In early stages, the treatment increases the vulnerability of cancer cells to numerous other drugs. Newark, New Jersey-based Rafael Pharmaceuticals is testing this treatment in pancreatic cancer and in acute myeloid leukemia.

At SBU facilities, Sasson explained that researchers and clinicians are taking a multidisciplinary approach in their work. One study, he said, is exploring the effects of a kind of radiation therapy for a subpopulation of pancreatic cancer that combines expertise in radiology, gastroenterology, pathology and medical and surgical oncology.

Sasson himself is interested in screening and biomarkers. At least half of his work is related to pancreatic cancer. When he thinks about people who have battled pancreatic cancer, several patients come to mind. He had a patient who was about 80 at the time of his diagnosis. His primary doctor told him to get his affairs in order.

“We operated on him and he lived another six or seven years,” Sasson recalls. “He was grateful to see his grandchildren graduate and to see his great-grandbabies being born.”

While every patient is unlikely to have the same outcome, Sasson said surrendering to the disease and preparing for the inevitable may not be the only option, as there may be other courses of action.

Another patient had advanced pancreatic cancer for 18 months before Sasson met her. She had received no treatment and yet the cancer didn’t progress, which is “almost unheard of and unbelievable.” In fact, the case defied medical expectations so dramatically that the doctors conducted two more biopsies to confirm that she had pancreatic cancer. “She did well for many years despite having advanced pancreatic cancer.”

In another case, a patient was receiving surveillance for lung cancer every three months. In between those visits, he had developed metastatic pancreatic cancer. This patient example and the previous one show the range of cancer progression.

The value of having an integrated clinical and research program is that scientists can look for subtle clues and signals amid the reality of cancer with a wide range of outcomes. Indeed, scientists attend the weekly tumor board meeting, so they can learn about the clinical aspects of the disease. Doctors also attend research collaborations so they can hear about developments in the lab.

Rather than dictating how researchers and clinicians should collaborate, Sasson hopes to facilitate an environment that sparks these partnerships.

Sasson joined Stony Brook Medical School almost three years ago. He said he is “impressed with the caliber of physicians.” It took time to get the critical mass and organization for pancreatic cancer to match the number of basic science investigators.

“I’m hopeful for the progress we’ll be able to make to treat this terrible disease,” he said.

Port Jefferson Village snatched ownership of the Village Cup back from John T. Mather Memorial Hospital at the 7th annual Village Cup Regatta boat race on Sept. 10 in Port Jefferson Harbor.

The race, which is presented by the Port Jefferson Yacht Club, features about a dozen competing boats representing either the village or Mather Hospital, and is held for a good cause.

The event has raised more than $300,000 since its inception for Mather’s Palliative Medicine Program and the Lustgarten Foundation, which funds pancreatic cancer research.

The hospital held the cup entering the 2016 race, though the village has now won four of the last six years.

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Port Jefferson Yacht Club hosted its sixth annual Village Cup Regatta on Saturday, raising funds for pancreatic cancer research through the Lustgarten Foundation and for John T. Mather Memorial Hospital’s palliative medicine program.

The regatta pits the hospital and Port Jefferson Village against one another in a friendly competition for the Village Cup, a trophy which the hospital has now won two years in a row following a village reign of three years.

Participants raised about $64,000 for the cause through this year’s race, according to yacht club member Chuck Chiaramonte. The sum will be split between the Lustgarten Foundation and the palliative care program, which is focused on improving patients’ quality of life.

Chiaramonte said over the six years of the regatta, the event has raised more than $300,000.

The yacht club — formerly known as the Setauket Yacht Club — supplied the boats and captains for the event, which included a parade of boats, games and face painting for children at the harborfront park, and a trophy presentation at the adjacent Village Center.

Chiaramonte said the club looks forward to the event every year.

“It was really meant to just be a joyous occasion and share the love of the water and boating with our neighbors,” he said.

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