O-PDX models are better than traditional PDX or CDX models  because they are more clinically relevant models1-4 that:  

  • Preserve the histological architecture, stroma construction5-8, and gene-expression or mutation status of the original tumor tissue.7-10 
  • Replicate the human tumor microenvironment, which is critical to cancer progression and metastasis.5
  • Can predict the development of resistance to first-line therapy and response to second-line therapy – before these events are observed in patients.7,11 

Orthotopic PDX models have gained prominence in basic and translational cancer research.5,12 

1 Byrne AT, Alférez DG, Amant F, et al. Interrogating Open Issues in Cancer Precision Medicine with Patient-Derived Xenografts. Nat Rev Cancer. 2017;17(4):254-268.
2 DeRose YS, Wang G, Lin YC, et al. Tumor Grafts Derived from Women with Breast Cancer Authentically Reflect Tumor Pathology, Growth, Metastasis and Disease Outcomes. Nat Med. 2011;17(11):1514-1520.
3 Joo KM, Kim J, Jin J, et al. Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ. Cell Rep. 2013;3(1):260-273.
4 Du Q, Jiang L, Wang XQ, Pan W, She FF, Chen YL. Establishment of and Comparison Between Orthotopic Xenograft and Subcutaneous Xenograft Models of Gallbladder Carcinoma. Asian Pac J Cancer Prev. 2014;15(8):3747-3752.
5 Long JE, Jankovic M, Maddalo D. Drug Discovery Oncology in a Mouse: Concepts, Models and Limitations. Future Sci OA. 2021;7(8):FSO737.
6 Nakano, K., Nishizawa, T., Komura, D., Fujii, E., Monnai, M., Kato, A., Funahashi, S. I., Ishikawa, S., & Suzuki, M. (2018). Difference in Morphology and Interactome Profiles Between Orthotopic and Subcutaneous Gastric Cancer Xenograft Models. J of Toxicologic Pathology, 31(4), 293–300.
7 Julien S, Merino-Trigo A, Lacroix L, et al. Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer. Clin Cancer Res. 2012;18(19):5314-5328.
8 Walters DM, Stokes JB, Adair SJ, et al. Clinical, Molecular and Genetic Validation of a Murine Orthotopic Xenograft Model of Pancreatic Adenocarcinoma Using Fresh Human Specimens. PLoS One. 2013;8(10): e77065.
9 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 Medulloblastoma. Neuro Oncol. 2012;14(5):574-583.
10 Shankavaram UT, Bredel M, Burgan WE, Carter D, Tofilon P, Camphausen K. Molecular Profiling Indicates Orthotopic Xenograft of Glioma Cell Lines Simulate a Subclass of Human Glioblastoma. J Cell Mol Med. 2012;16(3):545-554.
11 Tran Chau, V., Liu, W., Gerbé de Thoré, M., Meziani, L., Mondini, M., O’Connor, M. J., Deutsch, E., & Clémenson, C. (2020). Differential Therapeutic Effects of PARP and ATR Inhibition Combined with Radiotherapy in the Treatment of Subcutaneous Versus Orthotopic Lung Tumor Models. British J of Cancer, 123(5), 762–771.
12 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.