How are CDX Models Created?
CDX models are created by injecting human cancer cell lines into
immunodeficient mice. These mice lack a functioning immune system, which allows the human cancer cells to grow and form tumors without being rejected. The cells can be injected either subcutaneously or orthotopically, depending on the research goals.
Advantages of CDX Models
CDX models offer several advantages: Reproducibility: Because they are derived from established cell lines, CDX models provide consistent and reproducible results.
Simplicity: These models are relatively straightforward to generate and maintain.
Cost-effective: CDX models are generally less expensive to develop compared to other models like patient-derived xenografts (
PDX).
High Throughput: They allow for high-throughput screening of
drugs and other therapeutic agents.
Limitations of CDX Models
Despite their advantages, CDX models have several limitations: Lack of Tumor Heterogeneity: CDX models often lack the genetic diversity seen in human tumors, which can affect the relevance of the findings.
Absence of Immune Response: The immunocompromised state of the host mice means that CDX models cannot be used to study interactions between tumors and the immune system.
Microenvironment Differences: The tumor microenvironment in CDX models may not accurately replicate that of human cancers, potentially affecting the
translatability of results.
Applications of CDX Models
CDX models are widely used in various areas of cancer research: Drug Efficacy Testing: They are used to screen and evaluate the efficacy of new
anticancer drugs.
Mechanistic Studies: Researchers use CDX models to study the molecular mechanisms underlying cancer progression and treatment resistance.
Biomarker Identification: These models help in identifying potential
biomarkers for cancer diagnosis and prognosis.
Combination Therapies: CDX models are employed to investigate the potential benefits of combining different therapeutic agents.
Future Directions
While CDX models have been invaluable in cancer research, there is ongoing work to improve their relevance and utility: Humanized Mouse Models: Efforts are being made to develop humanized mouse models that can partially reconstitute the human immune system, allowing for the study of tumor-immune interactions.
Improved Cell Lines: The development of new, more genetically diverse cancer cell lines can help address the issue of tumor heterogeneity.
Integration with Other Models: Researchers are integrating CDX models with other preclinical models, such as
organoids and PDX, to provide a more comprehensive understanding of cancer biology.
Conclusion
Cell Line Derived Xenografts (CDX) remain a cornerstone in cancer research due to their reproducibility, simplicity, and cost-effectiveness. While they have certain limitations, ongoing advancements aim to enhance their relevance and applicability. CDX models continue to play a crucial role in drug development, mechanistic studies, and biomarker discovery, contributing significantly to our understanding of cancer and the development of new therapeutic strategies.
