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PATIENT DERIVED XENOGRAFTS
 

In the past years the majority of cancer research has been performed using traditional cancer cell lines to produce subcutaneous xenografts. These tumors are easy to establish but their clinical predictivity is poor due to two principal reasons. The first reason is related to the use of subcutaneous models because they lack the correct microenvironment for the cancer cells. This problem can be overcome by using orthotopic models where the cancer cells are inoculated into the correct microenvironment, or by using metastasis models, where cancer cells are inoculated into blood stream. These models are demanding for the drug candidate, but they have an excellent clinical predictivity. The second reason is related to the use of cancer cell lines. When cancer cell lines are expanded by culturing them in vitro, their gene expression profiles are changed, questioning the physiological relevance of traditional cell lines as sufficient models for cancer drug development.

Patient-derived xenografts (PDXs) are models where primary tumors are transferred from patients into immunodeficient mice. A clear benefit of PDX models against cell line based xenografts is their natural tissue architecture and composition, including the presence of cancer stem cells. Subcutaneous PDX models are today widely used in cancer research. They are expected to have substantially increased clinical predictivity over cell line based subcutaneous xenograft models.

Together with our partners Pharmatest offers a panel of more than 400 PDX models for cancer research. The PDX platform includes subcutaneous models for testing efficacy of novel drug candidates and identification of stratification biomarkers for targeted therapies. A database including molecular data of the tumors that are used in the PDX models, including gene expression profiles, mutations, and protein expression (such as hormone receptors, EGFR and resistance markers) is available through Pharmatest. Response data for hormonal therapies and chemotherapies of classical drugs and targeted drugs is also available.

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