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How liquid biopsies can change clinical practice in oncology.
Literature Information
| DOI | 10.1093/annonc/mdz227 |
|---|---|
| PMID | 31373349 |
| Journal | Annals of oncology : official journal of the European Society for Medical Oncology |
| Impact Factor | 65.4 |
| JCR Quartile | Q1 |
| Publication Year | 2019 |
| Times Cited | 187 |
| Keywords | cancer diagnosis, circulating free DNA, clonal evolution, liquid biopsy, minimal residual disease |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 0923-7534 |
| Pages | 1580-1590 |
| Issue | 30(10) |
| Authors | G Siravegna, B Mussolin, T Venesio, S Marsoni, J Seoane, C Dive, N Papadopoulos, S Kopetz, R B Corcoran, L L Siu, A Bardelli |
TL;DR
This review discusses the emerging role of circulating tumor DNA (ctDNA) as a non-invasive liquid biopsy tool for genotyping solid cancers, monitoring tumor dynamics, and detecting drug resistance, highlighting recent advancements in sensitivity and accuracy that could transform clinical practice. Although ctDNA has already been integrated into some treatment protocols, the paper emphasizes the need to address existing technical challenges for its routine clinical application, which could ultimately enhance treatment response monitoring and minimal residual disease detection post-surgery.
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cancer diagnosis · circulating free DNA · clonal evolution · liquid biopsy · minimal residual disease
Abstract
Cell-free DNA fragments are shed into the bloodstream by tumor cells. The analysis of circulating tumor DNA (ctDNA), commonly known as liquid biopsy, can be exploited for a variety of clinical applications. ctDNA is being used to genotype solid cancers non-invasively, to track tumor dynamics and to detect the emergence of drug resistance. In a few settings, liquid biopsies have already entered clinical practice. For example, ctDNA is used to guide treatment in a subset of lung cancers. In this review, we discuss how recent improvements in the sensitivity and accuracy of ctDNA analyses have led to unprecedented advances in this research field. We further consider what is required for the routine deployment of liquid biopsies in the clinical diagnostic space. We pinpoint technical hurdles that liquid biopsies have yet to overcome, including preanalytical and analytical challenges. We foresee how liquid biopsies will transform clinical practice: by complementing (or replacing) imaging to monitor treatment response and by detecting minimal residual disease after surgery with curative intent.
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Primary Questions Addressed
- What specific technical hurdles must be addressed to improve the routine use of liquid biopsies in clinical settings?
- How do liquid biopsies compare to traditional tissue biopsies in terms of accuracy and patient outcomes in oncology?
- In what ways can liquid biopsies be integrated into existing treatment protocols for various types of cancer?
- What potential ethical considerations arise from the widespread use of liquid biopsies in cancer diagnostics?
- How might advancements in liquid biopsy technology influence the future landscape of personalized medicine in oncology?
Key Findings
Research Background and Purpose
Cancer remains a leading cause of mortality globally, necessitating advanced diagnostic and monitoring techniques. Traditional tumor profiling through tissue biopsies is invasive and often fails to capture the dynamic nature of tumors due to heterogeneity and changes during therapy. Liquid biopsies, particularly through the analysis of circulating tumor DNA (ctDNA), offer a non-invasive alternative to monitor tumor dynamics, detect drug resistance, and guide treatment decisions.
Main Methods/Materials/Experimental Design
The review focuses on the methodology of liquid biopsies, particularly ctDNA analysis, highlighting advancements in sensitivity and specificity. Key methodologies include:
- Sample Collection: Blood samples are collected from patients to isolate ctDNA.
- ctDNA Isolation: Various techniques are employed to extract ctDNA, with plasma being preferred over serum to minimize contamination from cellular DNA.
- Analytical Techniques:
- Targeted Approaches: PCR-based methods (e.g., droplet digital PCR, Q-PCR) and next-generation sequencing (NGS) for specific mutations.
- Untargeted Approaches: Whole-exome and whole-genome sequencing for broader mutation detection.
- Data Analysis: Bioinformatics tools are utilized to interpret ctDNA sequencing data and correlate findings with clinical outcomes.
Key Results and Findings
- Sensitivity and Specificity: Recent improvements have led to high sensitivity (detecting mutations at low allele frequencies) and specificity (differentiating tumor-derived DNA from normal cfDNA).
- Clinical Applications: ctDNA has shown promise in:
- Genotyping tumors for targeted therapies.
- Monitoring minimal residual disease (MRD) post-surgery.
- Assessing treatment response dynamics earlier than traditional imaging methods.
- Resistance Mechanisms: ctDNA analysis can identify mutations associated with drug resistance, aiding in treatment planning.
Main Conclusions/Significance/Innovation
Liquid biopsies represent a transformative approach in oncology, offering a real-time, non-invasive method for monitoring tumor dynamics, guiding treatment decisions, and detecting drug resistance. The ability to assess ctDNA levels can significantly improve patient management by providing insights into tumor behavior and treatment efficacy.
Research Limitations and Future Directions
- Technical Challenges: Variability in ctDNA detection methods and the need for standardization remain significant barriers.
- Sensitivity Limitations: Early-stage cancers may not shed detectable levels of ctDNA, necessitating further technological advancements.
- Future Research: Emphasis on large-scale clinical trials to validate ctDNA applications in routine practice, with a focus on establishing standardized protocols for sample handling and analysis.
In conclusion, while liquid biopsies have the potential to revolutionize cancer diagnostics and treatment monitoring, ongoing research and technological improvements are essential to fully realize their clinical utility.
Literatures Citing This Work
- Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements. - Natalia O Tuaeva;Luca Falzone;Yuri B Porozov;Alexander E Nosyrev;Vladimir M Trukhan;Leda Kovatsi;Demetrios A Spandidos;Nikolaos Drakoulis;Alexandra Kalogeraki;Charalampos Mamoulakis;George Tzanakakis;Massimo Libra;Aristides Tsatsakis - Cells (2019)
- Therapeutic Approaches to Gastric Hepatoid Adenocarcinoma: Current Perspectives. - Jon Arne Søreide - Therapeutics and clinical risk management (2019)
- Why the Therapeutic Impact of RAS Mutation Clearance in Plasma ctDNA Deserves to Be Further Explored in Metastatic Colorectal Cancer. - Chiara Nicolazzo;Francesca Belardinilli;Salvatore Caponnetto;Angela Gradilone;Enrico Cortesi;Giuseppe Giannini;Paola Gazzaniga - Frontiers in oncology (2019)
- Hepatoid adenocarcinoma of the stomach: Thirteen case reports and review of literature. - Zheng-Rong Zhang;Jian Wu;Han-Wen Li;Tao Wang - World journal of clinical cases (2020)
- Sequential analysis of transcript expression patterns improves survival prediction in multiple cancers. - Jordan Mandel;Raghunandan Avula;Edward V Prochownik - BMC cancer (2020)
- Circulating tumor cells as Trojan Horse for understanding, preventing, and treating cancer: a critical appraisal. - Alexios-Fotios A Mentis;Petros D Grivas;Efthimios Dardiotis;Nicholas A Romas;Athanasios G Papavassiliou - Cellular and molecular life sciences : CMLS (2020)
- ESR1 Mutation Detection and Dynamics in Meningeal Carcinomatosis in Breast Cancer. - Marcela Carausu;Samia Melaabi;Jean-Yves Pierga;François-Clément Bidard;Luc Cabel - Journal of breast cancer (2020)
- Early circulating tumour DNA kinetics measured by ultra-deep next-generation sequencing during radical radiotherapy for non-small cell lung cancer: a feasibility study. - G M Walls;L McConnell;J McAleese;P Murray;T B Lynch;K Savage;G G Hanna;D Gonzalez de Castro - Radiation oncology (London, England) (2020)
- State of the Science and Future Directions for Liquid Biopsies in Drug Development. - Preeti Narayan;Soma Ghosh;Reena Philip;J Carl Barrett;Robert T McCormack;Justin I Odegaard;Geoffrey R Oxnard;Laurel J Pracht;P Mickey Williams;Gary J Kelloff;Julia A Beaver - The oncologist (2020)
- Potential treatment strategy for the rare osimertinib resistant mutation EGFR L718Q. - Yang Song;Ziqi Jia;Yadong Wang;Yanyu Wang;Peng Liu;Shuyang Zhang;Zhongxing Bing;Lei Cao;Zhili Cao;Elisabetta Rossi;Rita Zamarchi;Marc G Denis;Carlos Camps;Amaya B Fernandez-Diaz;Naixin Liang;Shanqing Li - Journal of thoracic disease (2020)
... (177 more literatures)
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