O-PDX models are better than traditional PDX or CDX models  because they are more clinically relevant models1 that:  

  • Preserve the histological architecture, stroma construction1, and gene-expression or mutation status of the original tumor tissue.2  
  • Replicate the human tumor microenvironment, which is critical to cancer progression and metastasis.3 
  • Can predict the development of resistance to first-line therapy and response to second-line therapy – before these events are observed in patients.4 

Orthotopic PDX models have gained prominence in basic and translational cancer research.3 

Burger, A M., Sausville, E A. Contributions of Human Tumor Xenografts to Anticancer Drug Development. Cancer Research. 2006;66(7):3351-3354. doi:10.1158/0008-5472.CAN-05-3627.  

Zhao X, Liu Z, Yu L, et al. Global gene expression profiling confirms the molecular fidelity of primary tumor-based orthotopic xenograft mouse models of medulloblastomaNeuro Oncol. 2012;14(5):574-583. doi:10.1093/neuonc/nos061. 

3 Killion, J J, Radinsky, R, Fidler, I J. Orthotopic Models are Necessary to Predict Therapy of Transplantable Tumors in MiceCancer Metastasis Rev. 1998;17:279–284 https://doi.org/10.1023/A:1006140513233

4 Das Thakur M, Salangsang F, Landman AS, et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistanceNature. 2013;494(7436):251-255. doi:10.1038/nature11814.