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The State of The Fight

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State of the Fight: Pancreatic Cancer

by Dr. Jeffrey Drebin, M.D., Ph.D., F.A.C.S.

State of the Fight: Pancreatic Cancer

What if you could starve one of the world’s deadliest cancers, effectively killing it before it could take another life?

In 2012, about 44,000 Americans will be diagnosed with cancer of the pancreas – a gland located in the abdomen. The disease will claim an estimated 37,390 lives, with a shockingly low five-year survival rate of only six percent. Pancreatic cancer is unique among the top-five cancer killers (lung, colorectal, breast, pancreas and prostate) in that both the incidence rate and death rate are increasing. It’s often a “silent killer,” difficult to detect until it’s too late due to a lack of specific symptoms. There isn’t much that known to be useful in terms of prevention beyond avoiding smoking and eating a healthy diet low in fat and high in fruits and vegetables. Clearly, something drastic has to be done.

As the John Rhea Barton Professor and Chair of the Department of Surgery at the Perelman School of Medicine of the University of Pennsylvania, and a member of the Cancer Service Line Executive Committee of the Abramson Cancer Center at Penn, I am just one among the many doctors worldwide determined to fight back against pancreatic cancer. My primary clinical focus is abdominal cancer surgery, and I perform about 120 major pancreas procedures each year. In addition, I am one of the co-leaders of our multi-disciplinary Gastrointestinal Cancer Program, and a member of the Stand Up To Cancer Pancreatic Cancer Dream Team.

Most patients who can be cured of pancreatic cancer are cured by surgery (in many cases, along with chemotherapy and/or radiation). Prior to the 1980s, surgery of the pancreas was extremely challenging and dangerous, with 25-30% of patients dying during or immediately after surgery. That number is now around 1% when the surgery is performed by experienced surgeons in high-volume centers. As our early results have improved, we are seeing more and more long-term survivors. Unfortunately many patients who undergo a “successful” surgical resection of their pancreatic tumor develop recurrent disease. So while the surgery may extend lives, it is often not curative. Furthermore, the majority of patients with pancreatic cancer are not diagnosed until their disease is too extensive to even allow an attempt at curative surgery.

We need to improve our ability to diagnose pancreatic cancer early. We need to understand why surgery fails to cure some patients while helping other. And we need better systemic therapies – treatments that use substances that travel through the bloodstream, reaching and affecting cells all over the body. Our SU2C Pancreatic Cancer Dream Team – consisting of physicians and scientists at multiple institutions, including Penn, Johns Hopkins, Memorial Sloan Kettering, Princeton, the Salk Institute and the Translational Genomics Institute – is addressing each of these challenges in a series of distinct clinical trials and correlative basic science studies.

We’re guided by advances in our understanding of tumor metabolism – exploring how pancreatic cancer cells obtain “fuel” to grow and spread. Recent studies have demonstrated that most cells acquire mutations that cause them to become “addicted” to the nutrients they need to grow and survive. In most cancers, this nutrient is glucose. But in pancreatic cancer, we’ve learned, it is glutamine. Cancers that use excess glutamine are often resistant to standard forms of chemotherapy, a key characteristic of pancreatic cancer. By developing tests that use advanced imaging techniques to determine which specific nutrients pancreatic cancer cells require to fuel their growth and survival, we will be able to develop therapies that can deprive pancreatic tumors of crucial nutrients – effectively “starving” the cancer cells to death.

Yet our work isn’t limited to nutrient deprivation. Our team also studies tumor specimens that are removed from patients to learn as much about their biology as possible. This includes DNA sequencing, studies of tumor metabolism, and studies of the tumor stroma – the “normal” cells that surround clusters of cancer cells and contribute to their growth. Our goal is to correlate these biologic factors with patient outcome. Additionally, we are conducting multiple pre-clinical and clinical trials of combinations of drugs that appear to be significantly more active at shrinking pancreatic cancer than standard treatments.

Our clinical trials of over 1000 patients have shown dramatic and sustained tumor shrinkage in certain patients with advanced disease. Where we used to talk about survival in weeks to at most a few months in patients with metastatic pancreatic cancer, over half of patients are surviving over a year. A substantial fraction of patients are surviving two years. In some cases, patients with tumors diagnosed as “inoperable” have had their tumors shrink enough to allow them to be surgically removed. We are already enrolling patients in new trials, adding additional targeted therapies to attempt to improve on these results.

Yet we’re still far from the goal of allowing most patients with cancer of the pancreas to have a normal life expectancy. Continued support for research is critical – both from the National Institutes of Health and from private organizations such as Stand Up To Cancer, the Lustgarten Foundation, and PanCan. We have more promising leads toward developing improved cancer treatments than at any time in history, but the costs of performing the laboratory and clinical research needed to develop such improved treatments are substantial. We owe it to the 94% of those 44,000 Americans facing a pancreatic cancer diagnosis who deserve not just a five-year window, but a lifetime to spend with their loved ones.

A native of Chicago, Illinois, Dr. Drebin received his M.D. and Ph.D. degrees from Harvard and performed his surgical training at the Johns Hopkins Hospital. He is involved in multiple organizations focusing on improving outcomes for patients with cancer, currently serving as Secretary of the Society of Surgical Oncology, Vice-President of the Philadelphia Academy of Surgery, President of the Society of Clinical Surgery, and as a member of the Board of Scientific Advisors of the National Cancer Institute. He has previously served on the Executive Committee of the American College of Surgeons Oncology Group and as Chair of the Pancreas Cancer Disease Site Sub-Committee of the Commission on Cancer of the American College of Surgeons. He currently serves as co-Principal Investigator on the Stand Up to Cancer grant supporting the Pancreas Cancer Dream Team.

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