By Mary Buschmann, PhD
November is Pancreatic Cancer Awareness month, and the Chicago evening skyline glows purple to honor those who have battled this grim disease. Pancreatic cancer is projected to be the second-leading cancer killer by 2030, but University of Chicago Medicine Comprehensive Cancer Center researchers are working to change that with a bold initiative to personalize care using genomic information.
Two years ago, Gordon Segal, the founder of Crate and Barrel stores, reached out to a multidisciplinary team of scientists and physicians at the University of Chicago, including genomics expert Kevin White, PhD, pancreatic cancer surgeon Kevin Roggin, MD, and geriatrician and social science researcher William Dale, MD, PhD.
Segal’s goal was ambitious – to cure pancreatic cancer.
Although Segal is an experienced and visionary businessman, he was motivated by something personal: the pancreatic cancer diagnosis of two close friends, one of whom lost her fight this past July.
Like Segal, anyone who has known a friend or relative with pancreatic cancer, or who has followed the fates of cultural icons Steve Jobs or Patrick Swayze, knows the rapid, lethal progression of this disease. The abysmal fact that only 6% of those diagnosed survive five years made his goal all the more lofty.
Together, White and Segal share a big idea to take on pancreatic cancer: personalized medicine. Their goal is to craft pancreatic cancer therapies based on an individual’s DNA, such that a treating physician could examine a patient’s genetic code, learn of unique genetic intricacies specific to the individual and their cancer, and select a therapy to aggressively target that patient’s disease.
With funding from Segal, combined with seed funding from the Michael Rolfe Pancreatic Cancer Foundation, the Chicago Pancreatic Cancer Initiative was born.
White, Roggin, and Dale had to overcome major hurdles to get their project off the ground. These included recruiting a larger team of clinical research specialists, bioinformaticians and clinicians; optimizing standard operating procedures for tumor collection, storage, and sequencing; and establishing the computing infrastructure to handle hundreds of terabytes of sequencing data.
Since the project’s inception, the team has worked tirelessly to build an effective strategy to bridge bench and bedside. In addition to using genomics data from DNA sequencing of patient tumors to identify novel biomarkers of disease and predictors of therapeutic success, they are also developing cost-effective, and reliable methods to screen patients at high risk for developing pancreatic cancer, and working to make existing treatments, such as surgery, safer.
The success of this strategy is reflected in the numbers. To date, over 150 pancreatic cancer patients at the University of Chicago Medicine have been enrolled in this study, resulting in over 300 banked tumor samples, with sequencing of these samples nearly complete.
These results are serving as a foundation for genomic pathologist Jeremy Segal, MD, PhD, to implement discoveries into diagnostic sequencing tools for oncologists across specialties at the University of Chicago Medicine. The current platform, named OncoScreen ST2.0, specifically identifies up to 50 of the most commonly mutated genes in cancer, with the number of mutations continuing to grow as new genetic variants are discovered. By summer, 2015, the Initiative plans to rollout a new diagnostic panel capable of identifying 1,200 mutations.
Furthermore, Dale and Roggin have continued their efforts to increase the number of patients eligible for pancreatic cancer resection surgery, which, despite being one of the few treatments that offers the promise to extend, if not save, a patient’s life, is associated with significant complication risks.
This past spring, Dale and Roggin reported in the Annals of Surgery that the use of physical and psychosocial assessment tools successfully predicted major surgical complications and outcomes following pancreatic cancer resection surgery. Armed with this information back in their clinics, they have revolutionized the way pancreatic cancer patients are identified for surgery, and ultimately, have made surgical treatment options a reality for more patients.
Although advanced genomics and novel predictive tools are at the heart of the scientific methods used by the team, extensive collaborations with outside institutions and foundations are akin to the arteries and veins.
Agreements are currently in place to sequence as many as 700 more patient tumors from Cleveland Clinic, NorthShore, Rush University Medical Center, and the extensive Pancreatic Cancer Action Network (PanCAN). Of note, PanCAN, through their Vision of Progress campaign, is utilizing the research and sequencing power of the Chicago Pancreatic Cancer Initiative in their goal to double pancreatic cancer survival rates by 2020.
The team is already looking toward the future at how their results will promote personalized patient care.
To accommodate the exponential increase in patient samples and sequencing data, hundreds of terabytes of computer storage space, at the price tag of over $200,000, is currently being installed.
Roggin and Dale are also in the planning stages with physicians at the University of Michigan and a nationwide oncology network to combine innovative computer platforms to use patient CT scans combined with their assessments to predict pancreatic cancer surgical outcomes.
Furthermore, a new collaboration with Northwestern University is underway using novel mouse models to predict how a patient’s genomic profile might determine chemotherapeutic success.
White concludes, “This is a very exciting time for the Chicago Pancreatic Cancer Initiative. Our team is in place and working well together. We have the technology and resources to analyze many, many more patient samples, and we have eager collaborators who share in our mission.”
Mary Buschmann, PhD, is the Research Project Manager for the Chicago Pancreatic Cancer Initiative between the University of Chicago Department of Medicine and the Institute for Genomics and Systems Biology.