After immunology, the next big game changer is going to be systems biology, integrating all these events at a convergence point that can be exploited therapeutically. We are at a period of tremendous opportunity in oncology and I’m very optimistic about the future.
—Alan F. List, MD
The Tampa Bay area of Florida is a haven for golfers and fishermen looking to unwind under the warm tropical skies. And the clean highways stretching through the scenic west coast of Florida are also a perfect excuse for weekend motorcycle enthusiasts, such as Alan F. List, MD, the President and CEO of Moffitt Cancer Center, to hit the road. “My wife and I both have Harley-Davidson motorcycles. I’d always wanted one and I was able to talk her into it, so about 8 years ago we bought a pair of Harleys, learned to ride, and now we go out together on weekends. It’s a lot of fun,” Dr. List told The ASCO Post.
A Father’s Influence
Dr. List grew up in York, Pennsylvania, a Pennsylvania Dutch community in the south-central region of the state, bordered by the Susquehanna River, which is the longest river on the East Coast. “I grew up in a very Germanic heritage. York is a nice place. In fact, it’s where the Harley-Davidson motorcycle was first made,” said Dr. List.
When asked about any early influences that might have affected his decision to pursue a career in medicine, Dr. List said without hesitation, “The one major influence on my decision to become a doctor and on my career was my father, who was a medic in World War II. He always told me that being a physician is the most rewarding thing that anyone could ever do, and he wanted me to consider medicine as a career. So, from the time I was a young boy, I had that thought lingering in the back of my head,” said Dr. List.
After high school, Dr. List entered Bucknell University, majoring in biology. “I had the opportunity to take advantage of what Bucknell called the ‘January Plan,’ which is a 6- to 8-week internship program, and did volunteer work in a hospital. I just loved it. My father’s enthusiasm for medicine coupled with the real-world experience in the hospital sealed the deal in my mind, and I decided to become a doctor,” said Dr. List.
Dr. List’s father also had advice for his son’s specialty. “My father wanted me to become a surgeon, a specialty he would have chosen given his experiences in combat, but he never had a chance to pursue a medical career after the War. At the end of my first year in college, I was exposed to the research lab and I ended up getting both my bachelor’s and master’s degrees by the time I graduated Bucknell in 1976. During my 4 years in college, I’d developed the bug for research, which essentially set my career path in motion. I wanted to do medicine but to combine it with clinical and laboratory research,” said Dr. List.
Captivated by Oncology
Dr. List continued, “In 1976, I enrolled in medical school at the University of Pennsylvania, which at the time had one of the best teaching curricula in the country. Although I’d had brief exposure to hematology and oncology during my years at Penn, it wasn’t a field that was on my radar screen at the time. I had a great experience at Penn, and after graduating, I headed west for my internship and residency in internal medicine at Good Samaritan Medical Center in Phoenix, Arizona,” said Dr. List.
It was during the early 1980s, around the time when clinicians and researchers were hoping that the miraculous activity of platinum drugs in testicular cancer would be a harbinger of a whole wave of active therapeutics. “It was a stimulating time when some of the most promising oncology research was being done, which was producing breakthroughs in cancer treatment. I was captivated by the progress and certainly wanted to be part of it,” said Dr. List.
Like many young doctors who have gone into the field of oncology, Dr. List was impressed by the resiliency and will of cancer patients. “I remember working on the oncology floor of the hospital and being truly inspired by the patients. Here you have people who are staring at their own mortality and yet they were so gracious for any help we could give them,” said Dr. List
Passion for Hematology
It was toward the end of his residency when Dr. List’s passion for hematology bloomed. “There was an attending physician at Arizona whom I was privileged to work with and learn from, Dr. Phil Scheerer, who was Phoenix’s first hematologist. What I loved about hematology—the way I was trained—was that you read your own bone marrows. So not only do you assess the patient and deal with the clinical issues, but as a hematologist you could serve as your own pathologist, categorizing and treating the disease, which gives you incredible insight into the biology of the disease,” said Dr. List.
About his early mentor, Dr. List commented, “Dr. Scheerer was an excellent bone marrow diagnostician and was not only a great clinician and caring with patients, but was also highly respected among all the oncologists and the few hematologists in the state.”
He continued, “As a researcher involved in myeloid malignancies, another intriguing characteristic of hematology was that you could actually access and study the disease through a bone marrow aspirate, which, in large part, was the aspect of hematology that eventually sold me on the field. After my residency program, I went to Vanderbilt University Medical Center in Nashville, Tennessee, to do a fellowship in hematology; the hematology and oncology programs were separate. As a hematology fellow, you read all the bone marrows with the attendings and spent a year reading out lymphomas, which at that time was with Dr. Bob Collins,” said Dr. List. “During my time at Vanderbilt, I became comfortable with pathology and trusted only my own interpretation, which would prove invaluable to my work in the research lab.”
Groundbreaking Research in Myelodysplastic Syndromes
After completing his fellowship, Dr. List joined the faculty at the University of Arizona. “When I arrived at the university, the diseases that weren’t covered by a program were myelodysplastic syndromes and acute myeloid leukemia (AML). And I felt they were terrific challenges, particularly myelodysplastic syndromes, so that’s the area I concentrated on,” said Dr. List.
Dr. List’s early research interest in AML focused on multidrug resistance. “We tested cyclosporine as a potential inhibitor of P-glycoprotein in the laboratory and then in a phase I/II study and took it to a phase III trial in Southwest Oncology Group, which to this day is the only phase III study in high-risk AML to show a survival benefit,” noted Dr. List.
Following the success with AML, Dr. List focused on myelodysplastic syndromes, which occupied much of his research efforts over the past 15 or so years. His curiosity eventually led his studies into the potential of antiangiogenic therapies in myeloid malignancies. “Angiogenesis inhibitors were first found to be important in solid tumors, but we were able to show that the blasts in myelodysplastic syndromes and AML not only express and secrete vascular endothelial growth factor (VEGF), but they also have receptors for VEGFR-1 and -2,” said Dr. List.
He explained that the early work led to the screening of several antiangiogenic agents, including some immunomodulatory drugs they received from Celgene Corporation. “We found that one drug was particularly effective in enhancing erythropoiesis in myelodysplastic syndromes, which was lenalidomide [Revlimid]. We took it to a phase I/II trial that led to the discovery of its activity in del(5q), and within 3 years, we completed a multicenter trial that led to the registration and U.S. Food and Drug Administration approval of lenalidomide in myelodysplastic syndromes,” said Dr. List.
Taking the Reins at Moffitt
Asked how a passionate research physician stepped out of the lab to become the President and CEO of a comprehensive cancer center, Dr. List responded, “I realized that to advance the field you need coordinated teams. I was very happy at the University of Arizona; however, when I visited Moffitt, I realized the uniqueness of its structure. All the departments are team- and disease-based on the clinical side regardless of your discipline, and I saw the opportunity for much broader collaborative work than I had at Arizona. So I came to Moffitt in 2003 as the Program Head of Malignant Hematology, and in 2008, I assumed the role of Physician-in-Chief, overseeing all the clinical science activities. And in 2011, I was proud to become the President and CEO of Moffitt.”
Asked how Moffitt is positioned in the current fiscal challenges of today’s health-care environment, Dr. List said, “We’re the third largest cancer center in the country, but we’re a young institution so we haven’t had time to build the philanthropic base and foundation support that older institutions do. Having said that, we’re doing well; in fact, for the past several years, we’ve been well ahead of budget. We’ve also focused on sponsored research agreements with pharmaceutical companies, which has helped us fund important research in a challenging funding climate at the National Institutes of Health. It’s been a healthy and creative partnership,” said Dr. List.
The launching pad for Dr. List’s career was in the hyperproductive 1980s, a true frontier land in oncology, when science, discovery, and drug development happened at breakneck pace. Retaining much of that original enthusiasm, Dr. List has high hopes for the potential of immunotherapy, but he feels the next paradigm change will occur in the intersection of science and technology. “After immunology, the next big game changer is going to be systems biology, integrating all these events at a convergence point that can be exploited therapeutically. We are at a period of tremendous opportunity in oncology, and I’m very optimistic about the future,” said Dr. List. ■