Detection of Chemotherapy-Resistant Pancreatic Cancer Using a Glycan Biomarker

A subset of pancreatic ductal adenocarcinomas (PDACs) is highly resistant to systemic chemotherapy, but no markers are available in clinical settings to identify this subset. We found that chemotherapy-resistant PDACs, but not chemotherapy-sensitive PDACs, express a glycan biomarker called sTRA. We confirmed the use of this marker to identify treatment-resistant PDAC in multiple systems: sets of 24 cell lines, 27 organoids, and isogenic cell lines; gene-expression signatures in primary tumors; tissue microarrays containing primary tumors; and blood plasma from cohorts of human subjects. These findings establish the use of tissue or plasma assays to identify the PDACs that are resistant to chemotherapy, which could improve the precision of systemic treatments and facilitate biomarker-guided trials targeting resistant PDAC. 27 pancreatic cancer cell lines with differing glycan status: sTRA positive (n=11), None (n=10), CA199 (n=3), and both sTRA & CA199 (n=3)