Poster Presentation 29th Lorne Cancer Conference 2017

Establishing human colorectal cancer patient derived xenografts for pre-clinical drug trials (#101)

Suad Abdirahman 1 , Adele Preaudet 1 , Akshay DCruz 1 , Oliver Sieber 1 , Tracy Putoczki 1
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

Colorectal cancer (CRC) is the third most common cancer worldwide and affects approximately 15,000 Australians every year. When the cancer is detected early, it is often resectable; however approximately 50% of the patients will experience a relapse and succumb to metastatic disease. Despite many advances in cytotoxic and targeted therapies in recent years, the development of resistance remains a challenge. Standard cell line xenograft models used to study it do not accurately recapitulate heterogeneous nature of the human disease, and as a result many pre-clinical drug targets fail in clinical trials. In addition, using cell lines in cell culture to determine the efficacy of new drug targets has revealed inconsistent results when compared to patient treatment response. As a result, the lack of appropriate animal models to accurately predict the response of anticancer drug targets limits most research opportunities. Our aim was to establish and characterise a series of CRC patient derived xenografts (PDXs) for use in anticancer drug studies. PDXs are physiologically relevant pre-clinical models where the patient tumour heterogeneity, genetic profile, and gene expression patterns are retained. PDXs were created when fresh human tumour samples were engrafted into immunocompromised mice directly after patient surgery. The tumour engraftment and growth rates of the PDXs were then monitored over time. Haematoxylin and Eosin staining, immunohistochemical staining and western blotting were used to compare the stability of the mouse tumours relative to the original patient tumours after serial transplantation. We have successfully generated 21 PDXs representing different stages of CRC samples. Our tumour engraftment rate is 70% following subcutaneous implantation and our preliminary histopathological analysis shows that the features of the original patient tumour are retained in the mouse xenografts after serial transplantation. Our established PDXs will serve as a platform to study the effects of novel targeted therapies.