Abstract
Abstract 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. In this study, we evaluate the role of sTRA, a glycan biomarker for PDAC, in predicting chemotherapeutic responses. We tested the correlation between chemosensitivity and glycan expression in PDACs in multiple systems including sets of cell lines, organoids, and isogenic cell lines; primary tumors; and blood plasma from human subjects. The sTRA-expressing models tended to have stem-like gene expression and the capacity for mesenchymal differentiation, in contrast to the non-expressing models. The sTRA cell lines also had significantly increased resistance to seven different chemotherapeutics commonly used against pancreatic cancer. Patients with primary tumors that were positive for a gene-expression classifier for sTRA received no statistically significant benefit from adjuvant chemotherapy, in contrast to those negative for the signature. In another cohort, based on direct measurements of sTRA in tissue microarrays, the patients who were high in sTRA again had no statistically significant benefit from adjuvant chemotherapy. Furthermore, a blood-plasma test for the sTRA glycan identified the PDACs that showed rapid relapse following neoadjuvant chemotherapy. This research demonstrates that a glycan biomarker could have value to detect chemotherapy resistant PDAC in clinical settings. This capability could aid in the development of stratified treatment plans and facilitate biomarker-guided trials targeting resistant PDAC. Citation Format: ChongFeng Gao, Luke Wisniewski, Ying Liu, Ben Staal, Ian Beddows, Dennis Plenker, Mohammed Aldakkak, Johnathan Hall, Daniel Barnett, Mirna Kheir Gouda, Peter Allen, Richard Drake, Amer Zureikat, Ying Huang, Douglas Evans, Aatur Singhi, Randall Brand, David Tuveson, Susan Tsai, Brian Haab. Detection of chemotherapy-resistant pancreatic cancer using a glycan Biomarker [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-002.
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