Brian Haab. Ph.D., Head of Van Andel Institute’s Laboratory of Cancer Immunodiagnostics, will lead the five-year study in collaboration with David Smith, Ph.D. of Emory University. The team also includes researchers from Fred Hutchinson Cancer Research Center, Palo Alto Research Center, University of Georgia and University of Pittsburgh Medical Center.
About pancreatic cancer
Because of its tendency to spread prior to diagnosis and a resistance to chemotherapy, pancreatic cancer has one of the poorest survival rates of any major cancer. According to the NCI, pancreatic cancer will strike more than 43,000 Americans in 2012 and kill more than 37,000.
The search for new biomarkers
The term “biomarker” refers to a measurable characteristic that reflects the severity or presence of a disease state. In this case, researchers will be looking for the presence of carbohydrates in the bloodstream as an indicator of pancreatic cancer.
“One of the most common features of pancreatic cancers is the increased abundance of a carbohydrate structure called the CA 19-9 antigen,” said Haab. “This carbohydrate structure is attached to many different proteins, many of which are secreted from the tumor into the blood circulation, making it available for detection as a biomarker.”
The limitations of current biomarkers
The detection of CA 19-9 from blood samples is widely used for confirmation of a diagnosis of pancreatic cancer and to get information about disease progression. Unfortunately, the test is not useful for early detection or diagnosis because about 20-30% of incipient tumors produce low levels of CA 19-9.
“The low levels are usually due to inherited genetic mutations in the genes responsible for the synthesis of CA 19-9,” said Haab. “However, patients who produce low CA 19-9 produce alternate carbohydrate structures that are abnormally elevated in cancer.”
Characterizing and identifying these alternate carbohydrate structures known as glycans is the focus of the new study, which could lead to an improved ability to detect cancer in the CA 19-9-low patients.
Making use of new developments in glycobiology research
The project will make use of several new developments to address the problem of identifying the diagnostic glycans in CA 19-9-low patients. These involve the use of affinity reagents for detecting specific glycan structures and the use of a class of proteins called lectins.
The project also involves work with so-called “shotgun glycomics,” in which all the glycans from a biological sample are tagged with a lipid-linked fluorescent tag and separated from each other to create a tagged glycolipid library, and will be guided through gene expression studies on the tumor tissue.
“We anticipate these new approaches advancing pancreatic cancer diagnostics as well as benefitting other glycobiology research in cancer,” said Haab.
Van Andel Institute
Established by Jay and Betty Van Andel in 1996, Van Andel Institute is an independent research organization dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process. This is accomplished through the work of over 200 researchers in more than 20 on-site laboratories and in collaborative partnerships that span the globe.
