2269P - Patient derived xenografts generated from circulating cancer stem cells on chorioallantoic membrane as an alternative pre-clinical model for personalized medicine in pancreatic cancer

Background

Although there have been improvements in the treatment of pancreatic cancer in recent years, the prognosis for this disease remains poor, with an overall 5-year survival rate of less than 10%. Therefore, new therapies and preclinical models are urgently needed. Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSC) are good candidates for generating preclinical models, making it possible to follow up the spatial and temporal heterogeneity of tumor tissues. This method is a non-invasive liquid biopsy that can be obtained at any stage of the disease. In this study, we sought to set up a novel model in which patient-derived xenograft can be generated 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 secondary microtumors.

Results

Herein, we report an innovative in vitro platform for cultivation of cCSCs from peripheral blood of pancreatic cancer patients. The number of tumorspheres increased significantly with 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 first histological analysis suggests that the main histopathological features closely resemble the original pancreatic tumors.

Conclusions

The number of tumorspheres is associated with some clinicopathological parameters, but further follow-up is needed to evaluate the prognostic significance of tumorsphere detection in pancreatic cancer. PDXs generated from cCSCs on CAM membrane offer a promising approach for personalized medicine in pancreatic cancer, providing a platform for the study of individual patient tumors and the development of more effective treatments.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.