Patient-Derived Xenograft (PDX) models are xenografts developed directly from primary human tumoral tissue. A surgical resection is performed as part of a cancer patient’s treatment plan, and a xenograft is created using a portion of the removed tissue. In a typical PDX model, the freshly excised tumor fragment is broken up into small pieces or dissociated into a single cell solution, and then implanted into the subcutaneous tissue (or at the original site in case of orthotopic implantation) of an immunocompromised mouse.
Over successive passages and transplants, the PDX model stabilizes, keeping the genomic, phenotypic, and molecular characteristics of the original human tumor. Passage numbers are limited to minimize tumor adaptability to the mouse host and maintain the PDX as near to the patient as feasible.
Because low passage PDX preserves tumor heterogeneity, key mutations, cellular architecture and a comparable responsiveness to therapy, it may be a better mimic of the original patient’s tumor. As a drug research tool, PDX are therefore believed to be more translational. For most of our PDX, a clinical history is accessible. For instance, tumors from patients who have already received first-line therapy can be chosen to test a novel medication intended for use in the event that first-line therapy is unsuccessful.
Key advantages of PDX models:
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Preservation of human tumor characteristics:
PDX models retain the genetic and phenotypic features of the patient’s original tumor, including mutations, gene expression profiles, and histological features, which makes them more predictive of human clinical responses compared to traditional cell line models.
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Tumor heterogeneity:
PDX models maintain the tumor heterogeneity seen in patients, which is critical for studying the complexities of cancer, including rare subpopulations of cells that might drive resistance to therapy.
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Evaluation of novel therapies:
These models offer a platform for preclinical testing of novel therapeutic strategies, including targeted therapies, immunotherapies, combination treatments, and chemotherapies. PDX models can be used to identify the most promising therapeutic candidates, predict patient responses, and also identify potential resistance mechanisms.
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Immune microenvironment representation:
While PDX models are typically created in immunocompromised mice, recent advancements allow for the development of humanized PDX models, which incorporate human immune cells. These models can be particularly valuable for testing immunotherapies, such as immune checkpoint inhibitors, and studying interactions between the tumor and the immune system.
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Cryopreservation of tumor fragments:
Tumor fragments from each successive passage of a PDX model can be cryopreserved for future studies. This enables the development of models that can be easily re-established for additional investigations.
To learn more about our PDX offerings or to discuss your specific research needs, please contact us.