Patient-derived subrenal capsule xenografts remain stable after multiple passages, enabling preclinical assessment of novel anticancer drugs — The Association Specialists
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Patient-derived subrenal capsule xenografts remain stable after multiple passages, enabling preclinical assessment of novel anticancer drugs (255)

Aiqun Xue 1 , Sohel M Julovi 2 , Jaswinder S Samra 1 , Anthony J Gill 1 , Matthew Wong 2 , Thomas J Hugh 1 , Ross C Smith 2
  1. Royal North Shore Hospital, Sydney, NSW, Australia
  2. The University of Sydney, Sydney, NSW, Australia

Objective: The keys of causing low success rate of oncology drug development by traditional cell lines-derived preclinical models have been well discussed (1). Thus, a recent increase in the use of patient-derived tumour xenografts (PDTX), which has demonstrated more faithfully recapitulate the molecular diversity, heterogeneity and histology in human tumours (2).We have successfully developed PDTX models engrafted fresh tumour tissue into subrenal capsule of immunosuppressed mice (3). In this project, we studied the stabilisation of this new preclinical model for developing of novel therapeutics.
Methods: PDTX models were established by implanting fresh patient pancreatic cancer (PC) underneath the capsule of kidneys of NOD/SCID mice and passaged in mice up to 5 generations. The stabilisation of generations of PDXT model was examined by histology and molecular biomarkers. We also have utilized these models to test the responses to the combination of anticancer drugs.
Results: The passaged 5 generations of PDXT tumour grafts showed a similar histological architecture and morphology with more than 95% engrafting rate. Those 5 generations of tumour grafts also consistently expressed a similar level of proliferation marker Ki-67, cytokeratin 7/20, especially the genetic marker Smad4. With four stable passaged tumour PDXT grafts, three tumours did not responded neither to Gemcitabine treatment alone nor to the combine treatment with Erlotinib. However, the one PDXT model showed the response to Gemcitine treatment, but not in combine treatment with Erlotinib. It suggests that personalised treatment needed to be optimised.
Conclusion: The generations of PDXT xenografts by reimplantation successive generations of mice are biological stable in molecular and genetic levels. The ability to stably passage patient’s fresh tumour tissue into large numbers of mice provides possibilities for better prediction of personalised treatment and, consequently, better outcomes for cancers compared with conventional cell line approaches.

  1. Tentler JJ, Tan AC, Weekes CD, et al., Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol. 2012 17;9(6):338-50.
  2. Jin K, He K,Teng F, et al., Heterogeneity in primary tumors and corresponding metastases: could it provide us with any hints to personalize cancer therapy? Personalized Medicine. 2011 8;(2): 175-182
  3. Xue A, Julovi SM, Hugh TJ,et al., Patient-derived first generation subrenal capsule xenografts of pancreatic cancer potential models for guidance of gemcitabine responsiveness. In writing.