UMHS researchers wage hope together against pancreatic cancer
Two decades ago, Howard Crawford, Ph.D., dedicated himself to basic science research exploring the biology of various cancers. Having already lost several members of his family to the disease, he immersed himself in the molecular nuances of many cancers, thinking that they were all alike.
“Then I learned the dismal statistics about pancreatic cancer,” said Crawford, now a professor of molecular & integrative physiology and internal medicine at the U-M Medical School. “I had never known anyone with pancreatic cancer, but I knew that’s where I needed to focus my research. Clearly, it wasn’t like all the rest.”
Today, Crawford directs one of the nation’s leading pancreas research programs here at U-M. What he learned 20 years ago — and what still drives him today — was this: mortality rates for pancreatic cancer are higher than all other common forms of cancer, and this year it surpassed breast cancer to become the third most common cause of cancer-related deaths. Only 8 percent of patients with pancreatic cancer live five years after diagnosis. 70 percent don’t survive a single year.
To put those statistics in perspective, an estimated 53,000 people in the U.S. will be diagnosed with pancreatic cancer this year, and nearly 48,000 will die from it, according to the National Institutes of Health.
November is National Pancreatic Cancer Awareness Month, and today marks World Pancreatic Cancer Day.
Hard to diagnose, harder to treat
The biology behind pancreatic cancer makes it a difficult disease to fight.
First, there are very few specific symptoms, meaning it usually goes undetected until the latest stages. The organ is located centrally within the body, making it a challenge to image, and there are no good blood tests for detection either.
Finally, most of the tumor is made up of dense scar tissue, impeding blood flow and blocking the delivery of therapeutic agents.
“This environment that forms immediately around the tumor, the ‘microenvironment,’ almost seems designed to block effective treatment,” Crawford said. “That’s where our work comes in, because the more we learn about pancreatic cancer, the more likely it is that we’ll learn how to attack it.”
Crawford has teamed with Marina Pasca di Magliano, Ph.D., associate professor of surgery and cell and development biology, along with other collaborators from the Pancreas Research Program, to devise a method of modifying the microenvironment of pancreatic cancers in such a way that immunotherapy — a type of treatment that uses a person’s own immune system to fight the disease — can become effective in overcoming pancreatic cancer.
“Immunotherapy has shown incredible promise in the treatment of other cancers. But the results in pancreatic cancer clinical trials have been disappointing. We aim to change that,” said Crawford.
Their ideas recently received support from President Barack Obama’s Cancer Moonshot initiative through a $500,000 supplement to the Cancer Center from the National Institutes of Health.
“Marina’s lab and my lab, working together, have found a potential solution that we hope will improve immunotherapy as a treatment in the future,” Crawford said. “We’re looking at using FDA-approved drugs in novel combinations with immunotherapeutic agents to help treat patients.
“We are in the early stages of testing these drug combinations in pancreatic cancer models, but the NIH support makes us feel like we’re on the right track and will allow us to continue moving forward.”
Racing against time
Crawford acknowledges that his current project will take time and may not be able to help those facing a recent diagnosis, a reality that is both difficult and motivating.
“You can’t help but grow close with some of the patients you come into contact with,” he said. “It’s impressive how strong they can be, but you often have to watch their health deteriorate, sometimes very quickly. Many of the patients I’ve become friends with have passed away in a very short period of time. I take them with me into the lab every day.”
What started off as an intellectual challenge 20 years ago is now a personal mission for Crawford. “Absolutely nothing we do, no matter how hard we work, is fast enough. But for all of those patients yet to be diagnosed, we are obligated to get it right.”