Innovative Glycoengineering Strategy Could Reveal New Biomarkers for Pancreatic Cancer

While the 5-year survival rate for pancreatic cancer has increased over the last decade to 13%, it continues to be one of the toughest cancers to diagnose and treat. One contributing factor is a lack of biomarkers for disease detection and treatment response. Biomarkers are measurable signs that coincide with biological processes, such as a protein that is only found in people with pancreatic cancer and decreases proportionally with tumor size. When identified, biomarkers can be used for diagnosis, characterization of types of cancer, decisions about which treatment may be beneficial, and can be used to monitor treatment response. 

A biomarker currently used for multiple cancers is carbohydrate antigen 19-9 (also called cancer antigen or CA 19-9) and is the only biomarker currently approved for identifying pancreatic cancer.  Research is focused on identifying new biomarkers for pancreatic cancer to facilitate early diagnosis, characterize different subsets of patients, and monitor disease progression. Howard Katz, Professor of Materials Science and Engineering at Johns Hopkins University and a 2017 Hirshberg Foundation Seed Grant Awardee in collaboration with Kevin Yarema, Associate Professor of Biomedical Engineering at Johns Hopkins University, have turned to an emerging technique called glycoengineering to identify novel biomarkers for pancreatic cancer. This work is detailed in their recent Journal of Biological Chemistry publication titled Profiling the pancreatic cancer secretome with metabolic glycoengineering. 

Metabolic glycoengineering is the process of introducing non-natural sugar molecules to cells. Cells then use these sugars in biochemical pathways to make proteins; these new proteins are tagged with the synthetic sugar molecules and are used to make cellular components or can be secreted. Katz and Yarema’s groups used this technique to identify all the proteins secreted (called the secretome) by pancreatic cancer cells, identifying several proteins as potential biomarkers. Research is continuing to evaluate the use of the identified proteins as biomarkers for pancreatic cancer and specifically for early disease. An important and unanticipated aspect of this study was that their method increased the production of extracellular vesicles by the cells. As extracellular vesicles have therapeutic potential, Katz and Yarema are also extending their research to ask whether this approach could be used as a theranostic (a technique that combines diagnostic and therapeutic capabilities) strategy.

Though Dr. Katz’s research has mainly focused on electronic material chemistry; he has been driven to find ways to use his training to increase early detection of pancreatic cancer by personal experiences of friends and family with the disease. Through collaboration with Dr. Yarema, he has been able to leverage his experience and expertise to demonstrate the possibility of using this unique technique to identify and create new biomarkers for pancreatic cancer. On his 2017 Seed Grant, Dr Katz says “I am extraordinarily grateful to the Hirshberg Foundation for opening this opportunity to me and hopefully contributing to the urgently needed early detection and eventual eradication of pancreatic cancer.”

Research like this is possible because of donor support. Hirshberg Foundation Seed Grants give scientists the early funding needed to test bold ideas, generate critical data, and pursue discoveries that may otherwise go unexplored. Today’s Seed Grant projects lay the groundwork for tomorrow’s advances in pancreatic cancer detection, treatment, and survival.