Physician-scientist Ronald DeMatteo focuses on strategies to reduce immune subversion in gastrointestinal stromal tumor and liver cancer and on immunobiology in liver cancer. We spoke to him in 2008.
I remember wanting to be a surgeon by the time I reached high school. I grew up in Maryland and New Jersey with a mother who was a nurse and a father who worked in hospital administration, so it wasn’t a stretch for me to consider becoming a doctor. However, my grandparents were immigrants from Italy, and I’m the first person in my family to get any kind of doctoral degree.
A critical moment came when I was in college at Johns Hopkins University. I wanted to get a flavor of surgery through some first-hand experience, so I started knocking on doors at Johns Hopkins Hospital.
After numerous rejections, I received an enthusiastic response from a very senior surgeon who had done exactly what I wanted to do — he had apprenticed himself to a surgeon while an undergraduate. He called the chief resident, Keith Lillemoe, and assigned me to him for the summer. Dr. Lillemoe had me observe operations and took me on rounds to see patients.
I went on to complete medical school at Cornell University Medical College, followed by seven years of residency training in surgery at the Hospital of the University of Pennsylvania. In 1997, I came to Memorial Sloan Kettering for a two-year fellowship with the goal of becoming a general surgical oncologist.
I never intended to specialize in surgery on the liver and pancreas. But about midway through my fellowship I had the chance to work with Leslie Blumgart [then Chief of Memorial Sloan Kettering’s Hepatobiliary Service]. He was a great mentor during that period and the years that followed, and the experience changed the trajectory of my career.
The techniques he brought to Memorial Sloan Kettering and refined here made this the premier place in the world for liver surgeries. He got me excited about doing liver surgery and was looking for another person to add to the service. This was an offer that no surgeon could refuse.
From a surgical point of view, the complexity of patient diseases at Memorial Sloan Kettering is unmatched. At most institutions, it is impossible for a cancer surgeon to be able to concentrate on just a few diseases and do a high volume of procedures. In a very short time, I gained a vast amount of surgical experience, particularly with liver and pancreas cancer.
Our group does more than 250 liver resections and 150 pancreatic resections a year, which makes us an international leader. Doing liver and pancreas surgery is very challenging because both organs are surrounded by major blood vessels. However, the techniques pioneered and improved at the Center help keep the operative risk quite low.
I think the next advance for oncological surgery will be finding ways to improve outcomes by integrating surgery with other treatments. This includes, for example, new radiation techniques, such as intraoperative radiation, which allows treatment to be delivered to patients while they are still in the operating room so they don’t need weeks of radiation following surgery. It also includes new chemotherapy drugs that selectively target cancer cells by taking advantage of molecular differences between these cells and normal cells.
For example, we’ve had a landmark success with a targeted molecular therapy called imatinib (Gleevec®) in a large, nationwide clinical trial sponsored by the National Cancer Institute. Patients who received Gleevec following surgery for a rare cancer called a gastrointestinal stromal tumor (GIST) were less likely to have a recurrence of their cancer compared with those who didn’t receive it.
In 2000, when Gleevec was first applied to GIST, I was working with Murray Brennan [former Chair of Memorial Sloan Kettering’s Department of Surgery] to develop the national trial. Eight years later, we have changed the standard of care in GIST. We’re hoping there will be more agents like Gleevec down the road for pancreas and liver cancer.
In addition to surgery, I conduct laboratory research. I learned the basics of immunology research during my residency at Penn and continued gaining expertise in the field after coming to Memorial Sloan Kettering.
Now I conduct research on dendritic cells, which are the master regulators of the immune system throughout the body and which have the potential to generate a strong immune response against cancer. Specifically, we’re focusing on the behavior of dendritic cells and other immune cells within the liver.
The liver is the most common site for metastatic disease. What could be the reason for this? By analyzing tissue specimens from surgical patients, we found that the dendritic cells within the liver are actually weaker than dendritic cells elsewhere in the same patient.
This discovery has implications for developing therapies that induce dendritic cells to be more active. We’ve been exploring such therapies in mouse models, and eventually, in collaboration with the Immunology Program at Memorial Sloan Kettering, we hope to move to human clinical studies.
Surgery and laboratory research are both very rewarding – but in different ways. Liver and pancreas surgery is technically challenging and can be instantly gratifying. But surgery is one patient at a time. Research is the opposite — it’s gratifying over years or even decades, and you have the chance to affect a lot of people with a new finding. I definitely see myself continuing to work in both.
Recently, I have had the opportunity to work closely with Peter Scardino [Chair of the Department of Surgery]. He has been a chair here and elsewhere for nearly two decades. I have learned an enormous amount about administration and leadership from him.
Another important role I have at Memorial Sloan Kettering is as a teacher and mentor to younger staff. I serve as director of the fellowship training program in general surgical oncology, and I formerly chaired Memorial Hospital’s Junior Faculty Council. The essence of academic medicine is tied to mentoring, and I try to put into practice what I learned from some of the masters of surgery – Drs. Blumgart and Brennan.
I find it very enjoyable to watch younger staff develop. Some of the best mentoring is when you don’t actually tell someone what to do but simply set an example of hard work or critical thinking that forces them to the next level in their development — not allowing them to settle for simply being adequate.
This high level of expectation is what makes Memorial Sloan Kettering exceptional. The tone is different from other hospitals, even down to the unit clerks. It’s a privilege to work here.