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The functional and clinical roles of liquid biopsy in patient-derived models.
Literature Information
| DOI | 10.1186/s13045-023-01433-5 |
|---|---|
| PMID | 37031172 |
| Journal | Journal of hematology & oncology |
| Impact Factor | 40.4 |
| JCR Quartile | Q1 |
| Publication Year | 2023 |
| Times Cited | 24 |
| Keywords | Liquid biopsy, Patient-derived organoid, Patient-derived xenograft |
| Literature Type | Journal Article, Review, Research Support, Non-U.S. Gov't |
| ISSN | 1756-8722 |
| Pages | 36 |
| Issue | 16(1) |
| Authors | Ziqing Zhu, Erya Hu, Hong Shen, Jun Tan, Shan Zeng |
TL;DR
This review highlights the significance of liquid biopsy in cancer research, focusing on the detection of circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles (EVs), while emphasizing the advancements in patient-derived xenograft (PDX) and organoid (PDO) models that enhance our understanding of tumor biology and treatment responses. The findings underscore the potential of these models in improving early cancer diagnosis, monitoring tumor burden, and facilitating drug testing, while also addressing the ongoing challenges and future directions in liquid biopsy research.
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Liquid biopsy · Patient-derived organoid · Patient-derived xenograft
Abstract
The liquid biopsy includes the detection of circulating tumor cells (CTCs) and CTC clusters in blood, as well as the detection of, cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) in the patient's body fluid. Liquid biopsy has important roles in translational research. But its clinical utility is still under investigation. Newly emerged patient-derived xenograft (PDX) and CTC-derived xenograft (CDX) faithfully recapitulate the genetic and morphological features of the donor patients' tumor and patient-derived organoid (PDO) can mostly mimic tumor growth, tumor microenvironment and its response to drugs. In this review, we describe how the development of these patient-derived models has assisted the studies of CTCs and CTC clusters in terms of tumor biological behavior exploration, genomic analysis, and drug testing, with the help of the latest technology. We then summarize the studies of EVs and cfDNA/ctDNA in PDX and PDO models in early cancer diagnosis, tumor burden monitoring, drug test and response monitoring, and molecular profiling. The challenges faced and future perspectives of research related to liquid biopsy using patient-derived models are also discussed.
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Primary Questions Addressed
- How do patient-derived models enhance the accuracy of liquid biopsy in identifying specific tumor markers?
- What are the limitations of using liquid biopsy in patient-derived models for early cancer diagnosis?
- In what ways can liquid biopsy contribute to personalized medicine through patient-derived models?
- How do the findings from CTC and cfDNA analysis in patient-derived models influence treatment strategies for cancer patients?
- What advancements in technology are necessary to improve the clinical utility of liquid biopsy in conjunction with patient-derived models?
Key Findings
Research Background and Purpose
Liquid biopsy has emerged as a minimally invasive method for cancer diagnosis and monitoring, focusing on the detection of circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs). This review discusses the functional and clinical roles of liquid biopsy in patient-derived models, specifically patient-derived xenografts (PDX), CTC-derived xenografts (CDX), and patient-derived organoids (PDO), to enhance understanding of tumor biology and improve cancer management.
Main Methods/Materials/Experimental Design
The review summarizes various studies employing PDX, CDX, and PDO models for analyzing CTCs, cfDNA/ctDNA, and EVs. Key methods include:
- Patient-Derived Xenograft (PDX): Tumor tissues from patients are implanted into immunocompromised mice.
- CTC-Derived Xenograft (CDX): CTCs isolated from patient blood are injected into mice to form tumors.
- Patient-Derived Organoid (PDO): Organoids are generated from patient-derived stem cells or tumor tissues.
Key Results and Findings
- CTC Studies: CTCs are identified as critical for understanding metastasis. PDX models provide a continuous source of CTCs, allowing for insights into their biological roles and mechanisms of metastasis.
- cfDNA/ctDNA Applications: cfDNA and ctDNA analysis helps monitor tumor burden and treatment response. Studies indicate that cfDNA levels correlate with tumor volume and can be used for early diagnosis.
- EVs as Biomarkers: EVs are recognized for their stability and role in cancer progression. They can differentiate between tumor and non-tumor sources, aiding in biomarker development.
Main Conclusions/Significance/Innovation
The review emphasizes that patient-derived models are valuable for studying the biology of CTCs, cfDNA/ctDNA, and EVs, thus facilitating the translation of liquid biopsy techniques into clinical practice. The integration of multi-omics approaches with these models enhances their utility in personalized medicine, allowing for better prediction of treatment responses and disease outcomes.
Research Limitations and Future Directions
- Limitations: The reliance on patient-derived tissues can limit the availability of samples, and the complexity of analyzing liquid biopsy materials can complicate results.
- Future Directions: More extensive studies are needed to standardize protocols for analyzing liquid biopsy components. Future research should focus on expanding the application of these models to various cancer types and integrating advanced technologies like CRISPR and high-throughput screening for drug testing.
| Aspect | Summary |
|---|---|
| Models Used | PDX, CDX, PDO |
| Key Findings | Insights into CTC biology, cfDNA/ctDNA for monitoring, EVs as biomarkers |
| Clinical Relevance | Potential for improved cancer diagnosis and personalized treatment |
| Limitations | Sample availability, analysis complexity |
| Future Directions | Standardization of protocols, broader cancer type applications |
This structured overview provides a comprehensive understanding of the functional and clinical roles of liquid biopsy in patient-derived models, highlighting their significance in advancing cancer research and treatment.
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Literatures Citing This Work
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