Why is pancreatic cancer so hard to kill?
It's a time of excitement in the world of cancer. For the first time in history, we seem to be making great strides in effective treatments. Immunotherapies that unleash the immune system on cancer are curing the disease in some patients and targeted therapies that block the roads a cancer takes to become an aggressive killer are helping scores of others live longer.
And yet, for patients with pancreatic cancer, these advances provide little but frustration. We regularly see patients who ask us for access to immunotherapy, or who want to be put on clinical trials for the newest targeted therapy in the hope that this will improve their outcomes. But so far, none of these new therapeutic options have hit the mark. Pancreatic cancer has not seen a game-changing new therapy in over 40 years.
Today pancreatic cancer is the third leading cause of cancer-related death in the United States. Only 20 percent of patients survive longer than 1 year, and only seven percent make it to five years (by comparison, nearly 90 percent of all breast cancer patients make it to 5 years).
What is it about pancreatic cancer that makes it different from other cancers and so impervious to our best therapies?
The pancreas is an organ that sits near the stomach and secretes digestive fluids into the small intestine and also regulates blood sugar by producing insulin. Cancers that develop in the pancreas create a sort of fortress around the tumor. In fact, when we remove a pancreatic tumor, only a small portion of the growth is actually made up of cancer cells with the remainder scar tissue and other cells or what we collectively call the tumor microenvironment.
Not only does this scar tissue prevent cancer therapies from reaching pancreatic cancer cells, it also creates a harsh living environment for the cancer. The scar tissue restricts blood flow to the tumor, which reduces the flow of oxygen and nutrients. Cells need oxygen and nutrients to grow, and cancer cells are particularly hungry for both.
Essentially, a cancer that develops in the pancreas "grows up" in an environment that is particularly difficult, even for a cancer cell. Since it is reared in a tough environment, the cancer itself becomes resilient, impervious to standard, immune and targeted therapies.
To treat pancreatic cancer, we need to fundamentally change the way we think about the disease. We must abandon earlier approaches or strategies that work for other cancers, and aim for something completely novel. We need to better understand why this cancer is so different and look for its Achilles Heel.
How does this inform our treatment of pancreatic cancer? Since the pancreas regulates blood sugar, 30% of patients who present pancreatic cancer have uncontrolled blood sugar levels. This could increase the nutrient supply to the tumor and encourage tumor growth, suggesting that careful blood sugar control is warranted.
A better understanding of how pancreatic cancer adapts to its harsh environment will likely lead to new treatment strategies that specifically target what pancreatic cancer does best – grow in a desert.
Jordan Winter, MD, is a practicing clinician and an Associate Professor of Surgery and Jonathan Brody, PhD is a Director of the Research Division and Professor of Surgery at Thomas Jefferson University, both are researchers at the Sidney Kimmel Cancer Center at Jefferson.
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