Patient derived xenograft

Patient-derived xenografts (PDX) are models used in cancer research where human cancer tissues are transplanted into immunodeficient mice or rats. This method is used to study the biology of cancer and to test potential anti-cancer drugs. PDX models are considered to be more representative of human cancers compared to traditional cell line-derived models, as they better preserve the histological and genetic characteristics of the original patient tumor.

Overview

Patient-derived xenografts are created by implanting tumor tissues from a cancer patient into an immunodeficient rodent, such as a mouse or rat. These animals lack a functional immune system, allowing human tissues to grow without being rejected. The implanted tumors can then be grown, studied, and used to test the efficacy of cancer therapies. PDX models are used in various stages of drug development and personalized medicine to evaluate the effectiveness and safety of new cancer treatments.

Advantages

The main advantage of PDX models is their ability to maintain the heterogeneity of the original tumor, including its complex microenvironment, which is crucial for understanding tumor growth, metastasis, and drug resistance. This makes PDX a valuable tool for translational cancer research, bridging the gap between preclinical studies and clinical trials. Additionally, PDX models can be used to study patient-specific responses to treatments, aiding in the development of personalized medicine.

Limitations

Despite their advantages, PDX models also have limitations. The process of engrafting human tumors into mice can be time-consuming and expensive. Moreover, the lack of a functional immune system in the host animals means that the role of the immune system in cancer progression and response to therapy cannot be directly studied in PDX models. Furthermore, the adaptation of human tumors to grow in a mouse environment may lead to genetic and phenotypic changes over time, potentially diverging from the original human tumor characteristics.

Applications

PDX models are used in various research and clinical applications, including:

• Drug discovery and development: Testing the efficacy and toxicity of new anti-cancer compounds.
• Personalized medicine: Evaluating the best treatment options for individual patients based on the response of their PDX models to different therapies.
• Biomarker discovery: Identifying biomarkers that predict response to treatment or disease progression.
• Cancer biology: Studying the mechanisms of tumor growth, metastasis, and drug resistance.

Future Directions

The field of patient-derived xenografts is continuously evolving, with efforts focused on overcoming current limitations and enhancing the utility of PDX models. Innovations such as the development of humanized mice, which are immunodeficient mice engrafted with human immune cells, aim to better mimic the human immune response within PDX models. Additionally, advances in genomic and transcriptomic profiling are enabling more detailed characterization of PDX models, further bridging the gap between preclinical research and clinical application.

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