“We’re able to interact in a synergistic way. Everyone knows what everyone else is doing.” Ben Z. Stanger, MD, PhD, Professor of Medicine, lights up when he talks about the pancreatic cancer research team at Penn. A gastroenterologist and basic scientist, rather than an oncologist, Dr. Stanger rarely meets the people who benefit from his work, yet, they drive his research.
He recalls the powerlessness he felt as a medical student when confronted with a patient with metastatic pancreatic cancer. Medical science at that time had little to offer. It was this moment that solidified for Dr. Stanger, “if I ever had a laboratory of my own, pancreatic cancer would be the focus.”
Today, Dr. Stanger leads the Abramson Cancer Center’s Pancreatic Cancer Research Center, a position he inherited from Robert H. Vonderheide, MD, DPhil, John H. Glick Abramson Cancer Center Professor, an expert in cancer immunotherapy who now directs Penn's Abramson Cancer Center.
The center evolved from a pancreatic cancer Translational Center of Excellence, one of several disease-focused efforts to bring Penn physicians and scientists together to solve a pressing problem. The problem, in pancreatic cancer, is growing incidence with few effective treatment options.
“When a lot of the progress was made in other cancers, pancreas cancer was left behind. Until 2010, there was only one chemotherapy and it didn’t work very well,” says clinical director Ursina R. Teitelbaum, MD, Deenie Greitzer and Daniel G. Haller Associate Professor. Since 2010, doctors have found new approaches that yield better outcomes for patients. They now can offer what Dr. Teitelbaum calls “a menu of options.”
A Menu of Options
On average, there are approximately 10 pancreatic cancer trials open at Penn at a given time — more than most other medical centers. The menu of options spans trials for patients with a new diagnosis to those whose cancer has or has not responded to therapy.
In addition, the center has plans to expand “early diagnosis” trials for patients who do not have pancreatic cancer but are at high risk based on family history or other clinical information.
The team stresses the importance of moving quickly when pancreatic cancer is suspected. They want to reach patients sooner, at diagnosis or before the side effects of treatment are too much to bear. Too often, people are referred too late to qualify for trials. “We want to see patients sooner. We’d like to see them when they’re still well. We have first-line studies, second-line studies — there are options,” says Dr. Teitelbaum.
As a reminder of hope, Dr. Teitelbaum keeps a wall of magnets from her patients’ travels. She wants her patients to live well, not just live. Living well means feeling well. Within the center, two dedicated palliative care oncology specialists meet with patients early on to address the side effects of treatment.
A New Way of Thinking
“The center provides a new way of thinking. We’re not going to move forward doing the same things we’ve always done. There needs to be a new approach to tackling a disease like this,” says Gregory L. Beatty, MD, PhD, Assistant Professor, who directs experimental therapeutics. A new way means new kinds of treatments.
For example, a pioneering study combines a targeted therapy with immunotherapy. This vaccine trial, led by Kim A. Reiss Binder, MD, Assistant Professor, offers a potentially better maintenance option for patients who have remained stable or improved on chemotherapy with platinum-containing drugs, part of the arsenal used to treat pancreatic cancer patients.
Attacking pancreatic cancer early is a resonating theme of the center. “We have a multi-disciplinary team”, says Major Kenneth Lee, IV, MD, PhD, Assistant Professor. “For the right patient, surgery can be a cure for this cancer. We have the technical expertise to accomplish this.” New research explores ways to boost immune response before surgery to prevent recurrence post-operation. “Recurrence is common. We need to identify patients early and combine multiple strategies to treat this disease,” adds Dr. Lee.
Another line of research explores the use of anti-CD40 drugs in combination with chemotherapy. This work builds on a landmark paper published in Science in 2011, co-authored by Drs. Beatty and Vonderheide. Their research established that immunotherapy could be used to make chemotherapy work better, and that drugs targeting the protein CD40 could be effective in treating cancer. The new trials are supported by the Parker Institute for Cancer Immunotherapy and led by Dr. Vonderheide and Mark H. O’Hara, MD, Assistant Professor.
Other studies focus on new ways to use radiation as a “cancer vaccine” to boost anti-tumor response and changing the milieu in which a cancer lives — the so-called “tumor microenvironment.” There is no shortage of innovative ideas.
Groundbreaking Science and Unique Resources
Solid lab science, much of it happening at Penn, underlies this research. Penn investigators are learning about what drives pancreas cancer to spread and how it can escape elimination by the immune system. For example, Dr. Stanger studies the cells within tumors to figure out why some cancers respond better to treatment. His lab looks at “hot” and “cold” tumor cells, and how they grow. This work relies on unique resources like the mouse hospital run by Cynthia L. Clendenin, VMD.
Also promising is liquid biopsy research that uses circulating DNA to find biomarkers of pancreatic cancer. Progress could lead to a less invasive, more sensitive way to detect and track pancreatic cancer. This work is led by Erica Carpenter, MBA, PhD, director of the Circulating Tumor Material Center, and Kenneth S. Zaret, PhD, Joseph Leidy Professor of Cell and Developmental Biology.