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Liquid Biopsy-Based Biomarkers of Treatment Response and Resistance.
Literature Information
| DOI | 10.1016/j.ccell.2020.03.012 |
|---|---|
| PMID | 32289272 |
| Journal | Cancer cell |
| Impact Factor | 44.5 |
| JCR Quartile | Q1 |
| Publication Year | 2020 |
| Times Cited | 178 |
| Keywords | circulating tumor DNA, circulating tumor cells, liquid biopsy, minimal residual disease monitoring, personalized cancer medicine |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 1535-6108 |
| Pages | 485-495 |
| Issue | 37(4) |
| Authors | Elaine Kilgour, Dominic G Rothwell, Ged Brady, Caroline Dive |
TL;DR
This study explores the use of liquid biopsies, particularly circulating tumor DNA and circulating tumor cells from blood samples, as predictive biomarkers for personalized cancer therapy and for monitoring treatment responses and minimal residual disease. The findings highlight the potential of liquid biopsies to improve early detection of disease recurrence, addressing challenges associated with traditional tumor biopsies.
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circulating tumor DNA · circulating tumor cells · liquid biopsy · minimal residual disease monitoring · personalized cancer medicine
Abstract
Predictive biomarkers aid selection of personalized therapy targeted to molecular alterations within an individual's tumor. Patients' responses to targeted therapies are commonly followed by treatment resistance. Here, we survey liquid biopsies as alternatives to tumor biopsies to assess predictive and therapy response biomarkers. We examine the potential of liquid biopsies to meet the challenges of minimal residual disease monitoring after curative intent treatment for earlier detection of disease recurrence. We focus on blood, the most commonly collected minimally invasive clinical sample, and on the two most widely studied assays, circulating tumor DNA and circulating tumor cells.
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Primary Questions Addressed
- What are the specific advantages of using liquid biopsies over traditional tumor biopsies in monitoring treatment response?
- How do circulating tumor DNA and circulating tumor cells differ in their ability to predict treatment resistance?
- What are the current limitations of liquid biopsy techniques in the context of minimal residual disease monitoring?
- In what ways can liquid biopsy biomarkers be integrated into existing treatment protocols for personalized therapy?
- How might advancements in liquid biopsy technology influence future cancer treatment strategies and patient outcomes?
Key Findings
Research Background and Purpose
The review discusses the evolving role of liquid biopsies in oncology, specifically focusing on circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) as biomarkers for predicting treatment response and resistance in cancer patients. The authors aim to evaluate the advantages of liquid biopsies over traditional tissue biopsies, particularly in the context of personalized therapy and monitoring minimal residual disease (MRD).
Main Methods/Materials/Experimental Design
The review synthesizes various methodologies and technologies used in liquid biopsy analyses, including:
- Sample Collection: Primarily blood samples, but also includes other biological fluids.
- ctDNA Analysis: Involves the extraction of ctDNA from plasma to assess somatic mutations, copy number alterations, and gene fusions.
- CTC Enumeration: Techniques for isolating and analyzing CTCs to evaluate their potential as prognostic and predictive biomarkers.
- Assay Technologies: Includes RT-PCR, droplet digital PCR (ddPCR), next-generation sequencing (NGS), and methylation profiling.
Key Results and Findings
- ctDNA as a Biomarker: ctDNA levels correlate with tumor burden and disease stage. The review highlights the sensitivity and specificity of ctDNA in detecting mutations associated with treatment resistance, particularly in non-small-cell lung cancer (NSCLC).
- CTCs and Treatment Monitoring: CTCs can provide insights into tumor heterogeneity and treatment response. The review discusses the challenges of isolating CTCs due to their rarity but notes their potential in assessing protein expression related to therapy resistance.
- MRD Monitoring: ctDNA has shown promise in predicting disease relapse post-treatment, with studies indicating earlier detection of relapse compared to conventional imaging methods.
Main Conclusions/Significance/Innovation
The review concludes that liquid biopsies, particularly ctDNA and CTCs, represent a significant advancement in precision oncology. They offer a minimally invasive alternative to tissue biopsies for real-time monitoring of treatment responses and detection of resistance mechanisms. The integration of these biomarkers into clinical practice could enhance personalized treatment strategies and improve patient outcomes.
Research Limitations and Future Directions
- Technical Challenges: The review acknowledges ongoing technical challenges in liquid biopsy assays, particularly with CTCs, which require robust platforms for accurate detection and characterization.
- Need for Validation: There is a need for larger prospective studies to validate the clinical utility of liquid biopsy assays across various cancer types.
- Future Applications: The authors suggest that liquid biopsies could also play a role in immunotherapy, particularly in identifying predictive biomarkers for immune checkpoint inhibitors. Ongoing research into the potential of other liquid biopsy specimens, such as tumor exosomes and circulating RNAs, is also encouraged.
Summary Table of Key Points
| Aspect | ctDNA | CTCs |
|---|---|---|
| Collection Method | Blood plasma | Blood samples |
| Analysis Techniques | RT-PCR, ddPCR, NGS | CellSearch, marker-independent methods |
| Clinical Application | Predicting treatment response, MRD | Monitoring treatment response, prognosis |
| Challenges | False positives due to CHIP, tumor types with low ctDNA shedding | Rare occurrence in blood, phenotypic heterogeneity |
| Future Directions | Immunotherapy biomarkers, early detection | Real-time drug testing, CTC-derived models |
This comprehensive review highlights the transformative potential of liquid biopsies in cancer management, paving the way for more personalized and effective treatment approaches.
Literatures Citing This Work
- Plasma-Derived Extracellular Vesicle Phosphoproteomics through Chemical Affinity Purification. - Anton Iliuk;Xiaofeng Wu;Li Li;Jie Sun;Marco Hadisurya;Ronald S Boris;W Andy Tao - Journal of proteome research (2020)
- Advances in the assessment of minimal residual disease in mantle cell lymphoma. - Dayoung Jung;Preetesh Jain;Yixin Yao;Michael Wang - Journal of hematology & oncology (2020)
- Challenges and achievements of liquid biopsy technologies employed in early breast cancer. - Alfonso Alba-Bernal;Rocío Lavado-Valenzuela;María Emilia Domínguez-Recio;Begoña Jiménez-Rodriguez;María Isabel Queipo-Ortuño;Emilio Alba;Iñaki Comino-Méndez - EBioMedicine (2020)
- Plasma miR-1247-5p, miR-301b-3p and miR-105-5p as potential biomarkers for early diagnosis of non-small cell lung cancer. - Xiaohan Dong;Minghui Chang;Xingguo Song;Shanshan Ding;Li Xie;Xianrang Song - Thoracic cancer (2021)
- An insight into small extracellular vesicles: Their roles in colorectal cancer progression and potential clinical applications. - Xuefeng He;Xinyang Zhong;Zijuan Hu;Senlin Zhao;Ping Wei;Dawei Li - Clinical and translational medicine (2020)
- Design and Clinical Application of an Integrated Microfluidic Device for Circulating Tumor Cells Isolation and Single-Cell Analysis. - Mingxin Xu;Wenwen Liu;Kun Zou;Song Wei;Xinri Zhang;Encheng Li;Qi Wang - Micromachines (2021)
- Circulating tumor cell profiling for precision oncology. - Mahmoud Labib;Shana O Kelley - Molecular oncology (2021)
- Detecting Resistance to Therapeutic ALK Inhibitors in Tumor Tissue and Liquid Biopsy Markers: An Update to a Clinical Routine Practice. - Paul Hofman - Cells (2021)
- Liquid biopsy enters the clinic - implementation issues and future challenges. - Michail Ignatiadis;George W Sledge;Stefanie S Jeffrey - Nature reviews. Clinical oncology (2021)
- Gene expression in circulating tumor cells reveals a dynamic role of EMT and PD-L1 during osimertinib treatment in NSCLC patients. - Aliki Ntzifa;Areti Strati;Galatea Kallergi;Athanasios Kotsakis;Vassilis Georgoulias;Evi Lianidou - Scientific reports (2021)
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