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Pathways to Discovery: Fall 2013

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Special Series: Personalized Medicine
The UCCCC is transforming the future of medicine by using genetic, social, and environmental factors to predict cancer risk and customize prevention and treatment strategies for our patients. In this installment of a special series on personalized medicine, we describe an example of how genomics–the study of the entire human genome–is revealing clues about the molecular underpinnings of cancer.

UCCCC Investigators Use Genomics to Unravel the Complexities of Pancreatic Cancer

There are not too many success stories in pancreatic cancer. Compared to other malignancies, pancreatic cancer is associated with poor overall survival rates––less than 15 percent at five years even when the cancers are diagnosed at an early stage. A multi-investigator team at the University of Chicago Medicine Comprehensive Cancer Center is trying to change this bleak outlook with a generous gift from Gordon and Carole Segal, the founders of Crate & Barrel. It was the diagnosis of two close friends within just a few weeks of each other last winter that led Gordon to reach out to his good friend, Kevin White, PhD, James and Frank Family Professor in Human Genetics and Ecology and Evolution and director of the Institute for Genomics and Systems Biology (IGSB).

The timing could not have been more perfect. Dr. White was already making headway in understanding pancreatic cancer after assembling a diverse and complementary set of clinicians and scientists, including pancreatic cancer surgeons Kevin Roggin, MD, associate professor of surgery, and Mark Talamonti, MD, professor of surgery and chairman of surgery at NorthShore University HealthSystem; aging and social science specialist William Dale, MD, PhD, associate professor of medicine; medical oncologist and pancreatic cancer expert Hedy Kindler, MD, associate professor of medicine; and computational biologist Robert Grossman, PhD, professor of medicine and chief informatics officer for the University of Chicago Biological Sciences Division.

This project largely originated from the Chicago Cancer Genome Project and seed funding from the Michael Rolfe Pancreatic Cancer Foundation that was awarded to Dr. Roggin to build a pancreatic benign and malignant tissue repository and corresponding database with clinical, molecular, and genomic data. Establishment of these invaluable and unique resources has been critical to identifying factors that impact how well older patients tolerate surgery and preoperative chemotherapy, such as physiological age rather than chronological age, and biological predictors of surgical outcome.

“We hope that these translational research projects can help us identify factors that can predict a patient’s response to both medical and surgical treatments for pancreatic cancer as well as help to identify novel therapeutic targets for innovative therapies,” said Dr. Roggin. “We also hope to be able to identify in advance which therapies will have the least side effects, thereby minimizing toxicities for patients, further individualizing therapies,” added Dr. Dale.

The funding from the Segals is providing a much-needed boost to the project at a critical time and is allowing the investigators to leverage the data and infrastructure they generated to seek answers to bigger questions. The team is further developing pancreatic cancer biomarkers predictive of treatment outcomes and toxicities, and analyzing patient and tumor genomes to identify novel therapeutic targets and minimize side effects. Dr. White and colleagues are also working to create a paradigm in which all pancreatic cancer patients seen at the University of Chicago Medicine and NorthShore will have their tumor genomes sequenced.

By assessing a large patient population and mining the rich, centrally located database, the team will be able to identify markers that predict whether tumors will progress to advanced cancer and stratify low- and high-risk groups of patients. One of the most exciting aspects of the project is that this model can be replicated nationwide and will place the University of Chicago Medicine among the national leaders in implementing genome-guided medicine to treat pancreatic cancer.

Making these data available to the entire research community is a key piece to the success of the initiative. Dr. Grossman has developed a cloud computing system, called the Bionimbus Protected Data Cloud, to manage and analyze the enormous amounts of data generated from tumor sequencing. The IGSB is the only “Trusted Partner” of the National Cancer Institute and serves as a repository and analysis hub for genome data associated with the Cancer Genome Atlas project.

“Combining the extensive tumor genome data with the clinical and physiological patient information we have, and making these data available to all pancreatic cancer researchers, will hopefully allow us to make discoveries that directly benefit patients,” said Dr. White.