Abstract A041: Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for monitoring disease burden in patients with pancreatic cancer

Abstract

Abstract Pancreatic cancer is a highly lethal disease that is often diagnosed at a late stage, when it has metastasized to other organs. Several therapeutic options have been shown to be effective at significantly shrinking the tumor and improving survival. Unfortunately, very few of these treatments lead to the total disappearance of tumor and therefore require changes to the treatment strategy. One of the challenges is rapidly identifying if a treatment works or when it stops working so patients can be switched to another regimen. Currently, the best blood-based marker for tracking disease burden in patients with pancreatic cancer is CA19-9. Unfortunately, 15-20% of pancreatic cancer patients do not have elevated levels of this marker with a disproportionate number of non-CA19-9 elevated cases being African American and Hispanic patients. In addition, changes in this marker do not always correlate with disease burden since there are other factors that can change CA19-9 levels. In this study, we have identified two blood extracellular vesicle (EV) based protein markers THBS2 (Thrombospondin 2) and ALPPL2 (Alkaline phosphatase, placental-like 2) that aid in monitoring pancreatic cancer disease burden in both CA19-9 secretors and non-secretors. We found that the number of THBS2+ or ALPPL2+ EVs was significantly higher in serum samples from patients with pancreatic cancer than those from healthy controls. The level of THBS2+ or ALPPL2+ EVs in patients with pancreatic cancer correlated with a patient's response to treatment. In patients who have elevated CA19-9, the level of THBS2+ or ALPPL2+ EVs correlates with the changes in CA19-9 upon treatment. In CA19-9 negative patients, the level of THBS2+ EVs or ALPPL2+ EVs correlates with the tumor size changes (RECIST response) upon treatment. Hence, EVs containing THBS2 or ALPPL2 can potentially serve as additional and more informative biomarkers for monitoring disease burden in patients with pancreatic cancer regardless of their CA19-9 status. This work was supported by the Flinn Foundation and the HonorHealth Research Institute). Citation Format: Kuntal Halder, Gayle Jameson, Erkut Borazanci, Amber Vrana, Derek Cridebring, Daniel Von Hoff, Haiyong Han. Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for monitoring disease burden in patients with pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A041.