Abstract B062: Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for disease monitoring in pancreatic cancer patients undergoing neoadjuvant therapy

Abstract CA19-9, a carbohydrate antigen, is commonly used for disease monitoring in patients with pancreatic ductal adenocarcinoma (PDAC). However, 15–20% of PDAC patients do not exhibit elevated CA19-9 levels, making it suboptimal for disease monitoring in those patients. Previously, we identified serum extracellular vesicle (EV) based ALPPL2 and THBS2 as highly accurate biomarkers capable of distinguishing PDAC, including early-stage disease (Stages I and II), from non-cancerous conditions and healthy controls. Moreover, changes in serum concentrations of ALPPL2+ and THBS2+ EVs significantly correlate with treatment response. In this study, we sought to further validate the clinical performance of circulating EV ALPPL2 and THBS2 using plasma samples from patients undergoing neoadjuvant therapy. We determined the concentrations of ALPPL2+ or THBS2+ EVs in plasma samples from healthy individuals and longitudinal samples from patients with PDAC who have undergone neoadjuvant treatment. The longitudinal samples were from 15 patients who were treated with three different neoadjuvant regimens for 3-7 months with monthly blood sample collection and CT scans. We found that the concentrations of ALPPL2+ and THBS2+ EVs in plasma samples were on average 8 and 9 times higher in PDAC patients than in the healthy controls, respectively. Correlation analysis showed that the concentrations of both ALPPL2+ and THBS2+ EVs significantly correlate with changes in CA19-9 for patients with elevated levels of CA19-9. Furthermore, changes in plasma ALPPL2+ and THBS2+ EV concentrations correlated with tumor size, as measured by standard RECIST criteria, regardless of CA19-9 status. Our data indicate that plasma extracellular vesicle associated ALPPL2 and THBS2 levels are elevated in patients with PDAC and that changes correlate with patient response to neoadjuvant treatment. We are in the process of further validating these markers through a prospective trial involving patients with PDAC who do not exhibit elevated CA19-9 levels. Citation Format: KUNTAL HALDER, Erkut Borazanci, Gayle Jameson, Daniel Von Hoff, Derek Cridebring, Haiyong Han. Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for disease monitoring in pancreatic cancer patients undergoing neoadjuvant therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B062.