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Patient-Derived Xenograft Models in Cancer Research: Methodology, Applications, and Future Prospects
Saeed Aslani1,2, Mohamed I Saad3,4,5
1Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.
Abstract:
Patient-derived xenografts (PDXs) have emerged as a pivotal tool in translational cancer research, addressing limitations of traditional methods and facilitating improved therapeutic interventions. These models involve engrafting human primary malignant cells or tissues into immunodeficient mice, allowing for the investigation of cancer mechanobiology, validation of therapeutic targets, and preclinical assessment of treatment strategies. This chapter provides an overview of PDXs methodology and their applications in both basic cancer research and preclinical studies. Despite current limitations, ongoing advancements in humanized xenochimeric models and autologous immune cell engraftment hold promise for enhancing PDX model accuracy and relevance. As PDX models continue to refine and extend their applications, they are poised to play a pivotal role in shaping the future of translational cancer research.
Insights
Patient-derived xenografts (PDXs) are crucial for cancer research, overcoming traditional model limitations. Advancements promise to improve PDX accuracy for better therapeutic development and preclinical studies.
Area of Science:
- Oncology
- Translational Cancer Research
- Preclinical Models
Background:
- Traditional cancer models present limitations in accurately reflecting human tumor heterogeneity and response to therapy.
- Patient-derived xenografts (PDXs) offer a more relevant alternative by directly using patient tumor tissues.
- PDXs are instrumental in advancing our understanding of cancer mechanobiology and treatment efficacy.
Purpose of the Study:
- To provide a comprehensive overview of patient-derived xenograft (PDX) methodologies.
- To highlight the diverse applications of PDXs in basic cancer research and preclinical studies.
- To discuss the future potential and ongoing advancements in PDX model development.
Main Methods:
- Engraftment of human primary malignant cells or tissues into immunodeficient animal models.
- Utilizing PDXs for investigating cancer mechanobiology and validating therapeutic targets.
- Employing PDXs for the preclinical assessment of novel treatment strategies.
Main Results:
- PDXs enable detailed study of tumor behavior and drug response in a living system.
- Validation of therapeutic targets and assessment of treatment efficacy are key outcomes.
- The chapter outlines the established utility and ongoing evolution of PDX models.
Conclusions:
- PDX models are essential tools in translational cancer research, bridging the gap between laboratory findings and clinical application.
- Ongoing advancements, including humanized xenochimeric models, are enhancing the predictive power of PDXs.
- PDXs are expected to significantly influence the future landscape of cancer research and drug development.
