By Deborah Borfitz 

February 11, 2025 | Two glycans are better than one when it comes to detecting pancreatic cancer that currently lacks a biomarker capable of accurately and reliably spotting the disease. The gold standard biomarker CA19-9, approved by the U.S. Food and Drug Administration (FDA) for monitoring response to treatment, correctly identifies only 44% of cases but the addition of CA199.STRA ramped that up to 71% while maintaining a low false positive rate in a recent case control study. 

The hope is that the dual biomarker assay will find clinical utility in another few years at an early enough point in the disease process to give patients the possibility of a cure, according to Randall E. Brand, M.D.,  professor of medicine at the University of Pittsburgh, academic director of the gastrointestinal division of UPMC Shadyside and co-lead on the rigorous, multi-laboratory study published in Cancer Letters (DOI: 10.1016/j.canlet.2024.217245). In clinical testing to date “things are definitely trending in the right direction,” says Brand. 

CA199.STRA was identified a decade ago in the lab of Brian Haab, Ph.D., professor of cell biology at the Van Andel Institute, who was acting on a hunch that glycans structurally related to CA19-9 might also be elevated in pancreatic cancer patients. He subsequently developed and patented the assay technology that involves an enzymatic preconditioning step to modify the glycan to make it detectable. 

The results of this study have shown that by itself, CA199.STRA functions “at least as well and probably better than the existing gold standard biomarker, CA19-9,” says Brand. The exceptionally high performance of the new two-marker assay has been repeatedly demonstrated in different settings, including at ReligenDx, certified under the Clinical Laboratory Improvement Amendments (CLIA) program. 

ReligenDx recently licensed the technology and will continue its validation work. The CLIA lab spent several years reproducing results achieved with Haab’s antibody microarray methods on its own microplate assays. This initial testing phase included control samples but expanded to 200 “brand new samples” sent to the lab in a blinded fashion, says Haab.  

The next step for Haab and Brand is to find out how the dual assay works for the intended clinical use. To that end, they have started testing samples from high-risk populations for developing pancreatic cancer including patients with hereditary predisposition for developing this malignancy or pancreatic cysts.  

Screening Potential

The goal here is to be able to detect pancreatic cancer before symptoms appear, says Haab. But addressing that question with research on people who don’t have cancer would require a huge study because only a small percentage of them would eventually get it over a long period of time. 

Published studies to date have all been done using samples taken at the time of diagnosis. Researchers are now moving to the analysis of samples collected from patients in large screening studies from a few months to a few years prior to their cancer diagnosis. “You can do a reasonably sized study and still look at the value of detecting in blood the presence of cancer before it is clinically evident,” Haab says. 

When tumors are smaller, they don’t secrete as many of the molecules of diagnostic interest, including CA19-9, adds Haab. It follows that the percentage of patients showing biomarker elevations is smaller the further ahead of diagnosis they are being measured.   

In the screening setting, a test need not be perfect but good enough to justify it being used—meaning, better than existing options. Encouragingly, he says, early unpublished studies show performance improvement with the addition of CA199.STRA holding up in the pre-diagnostic samples.