Abstract 6900: Patient-derived xenografts from circulating cancer stem cells and their potential utility in personalized medicine of pancreatic cancer

Abstract

Abstract Background: Pancreatic cancer carries a poor prognosis in the majority of patients, with an overall 5-year survival rate of less than 10%. Therefore, the development of new therapies and preclinical models is crucial and urgently needed. Circulating cancer stem cells (cCSCs) are a subset of circulating cancer cells that have stem cell-like properties and play a significant role in tumor progression, metastasis, and treatment resistance. Patient-derived xenografts (PDX) reflect the genotypic and phenotypic landscape of patients' cancers and are useful for drug screening, biomarker development, and preclinical evaluation of personalized medicine strategies. In this study, we describe a fast, simple, and cost effective method to generate PDX on Chorioallantoic Membrane (CAM) from circulating cancer stem cells. Methods: In this study, primary cultures from circulating cancer stem cells were established using sphere-forming assays from 30 patients with newly diagnosed pancreatic cancer. Subsequently, tumorspheres were transplanted onto the CAM membrane of fertilized chicken eggs to form patient- derived xenografts. Results: For the identification of cCSCs from peripheral blood of pancreatic cancer patients, an innovative in vitro sphere-forming assay was established. The number of tumorspheres was correlated with clinicopathological parameters like tumor size, lymph node involvement and grading status of the primary tumor. Implantation of tumorspheres onto the CAM was successful in ~90 % of the applied samples. The histological analysis suggests that the PDX tumors were morphologically and pathologically identical to primary tumor tissue. Conclusions: The number of tumorspheres was associated with clinicopathological parameters. Further follow-up is needed to evaluate the prognostic significance of tumorsphere detection in pancreatic cancer. Generation of PDX from cCSCs on CAM has a high success rate and may become an integral part of the drug development arena, including drug screening and biomarker development. Citation Format: Monika Pizon, Dorothea Schott, Andreas Ettner-Sittner, Benedikt J. Wagner, Katharina Pachmann, Thiha Aung, Christina Hackl, Silke Haerteis. Patient-derived xenografts from circulating cancer stem cells and their potential utility in personalized medicine of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6900.