Setting up a PDXO platform of pancreatic cancer with spatial -omics characterization

Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive biology and lethality. Due to a low success rate of current diagnostic and therapeutic approaches in clinic, there is an urgent need for preclinical research studies to investigate the underlying biology of this malignancy. This knowledge is indispensable to facilitate the development and validation of potential new therapeutic compounds. Superior to conventional biomedical research models, the focus of this study is on the development and use of a well-established patient-derived 3D model, mimicking the tumor as it is present in a human body.

Aims
The development and characterization of patient-derived organoids (PDO) and patient-derived xenografts (PDX) of PDAC. The models are extensively analysed using advanced histological methods such as BaseScopeĀ®, 3D imaging and DNA hotspot sequencing.


Results
10 established PDAC-PDO and their corresponding parental tumors are already validated using immunostainings and DNA hotspot sequencing. The latter confirms presence of tumor cells in the organoids. In addition, this study is the first to show in situ detection of important driver mutations of pancreatic cancer, like KrasG12D, both in parental tumor and PDO. Thus far, 5 PDX have been generated that will undergo similar analysis.


Conclusion
We have successfully started a pre-clinical screening platform for PDAC based on PDO and PDX. Altogether, spatial-omics analysis of both models can substantiate (1) resemblance to parental tissue and (2) spatial genomic characteristics associated with the type of model used. Ultimately, the screening platform can be used by pharmaceutical companies to facilitate oncological drug testing."

Authors

Ellis Michiels1, Nouredin Messaoudi2, Yves Heremans1, Philippe Giron3, Toon Janssens3, Kim Frederix4, Sarah Aerts4, Hendrik Reynaert2, Ilse Rooman1

Organisations

1Laboratory of Medical & Molecular Oncology, Vrije Universiteit Brussel, Jette, Belgium 2Department of Gastroenterology, UZ Brussels , Jette, Belgium 3Interuniversity Genomics High Throughput Core, UZ Brussels, Jette, Belgium 4Innoser NV, Diepenbeek, Belgium

Presenting author

Ellis Michiels, PhD, Vrije Universiteit Brussel
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