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Circulating tumor DNA and liquid biopsy in oncology. ​

Literature Information ​

DOI10.1038/s43018-020-0043-5
PMID35122035
JournalNature cancer
Impact Factor28.5
JCR QuartileQ1
Publication Year2020
Times Cited271
Keywordscirculating tumor DNA, liquid biopsy, tumor monitoring, clinical trials
Literature TypeJournal Article, Review
ISSN2662-1347
Pages276-290
Issue1(3)
AuthorsDavid W Cescon, Scott V Bratman, Steven M Chan, Lillian L Siu

TL;DR ​

This review highlights the rapid advancements in circulating tumor DNA (ctDNA) analysis for cancer detection, characterization, and monitoring, emphasizing its growing role as a diagnostic tool supported by clinical evidence. It calls for interventional clinical trials to fully realize the potential of ctDNA liquid biopsies in managing both solid and hematological malignancies, thereby advancing cancer care.

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circulating tumor DNA · liquid biopsy · tumor monitoring · clinical trials

Abstract ​

Techniques for analyzing circulating tumor DNA (ctDNA) to detect, characterize and monitor cancer have matured rapidly. An increasing body of clinical evidence is demonstrating the capabilities of this technology as a diagnostic test. The full potential of ctDNA liquid biopsy in the diagnosis, characterization and management of solid and hematological malignancies will be uncovered through interventional clinical trials evaluating clinical utility. In this Review, we discuss the current landscape of ctDNA liquid-biopsy applications across the cancer continuum and highlight opportunities for clinical investigation.

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Primary Questions Addressed ​

  1. What are the specific challenges in the implementation of ctDNA liquid biopsy techniques in clinical practice?
  2. How does the sensitivity and specificity of ctDNA liquid biopsy compare to traditional biopsy methods in various cancer types?
  3. In what ways can ctDNA analysis influence treatment decisions and patient outcomes in oncology?
  4. What are the potential ethical considerations surrounding the use of liquid biopsy technologies in cancer diagnosis and monitoring?
  5. How do interventional clinical trials currently shape the understanding of ctDNA's role in managing solid versus hematological malignancies?

Key Findings ​

Key Insights ​

1. Research Background and Purpose ​

Circulating tumor DNA (ctDNA) represents a promising biomarker in oncology, as it allows for non-invasive insights into the genetic alterations of tumors. The rapid evolution of techniques for analyzing ctDNA has ushered in a new era of liquid biopsy applications, aimed at improving cancer detection, characterization, and monitoring. The primary purpose of this review is to evaluate the current landscape of ctDNA technologies and their clinical utility across various types of malignancies, both solid and hematological, while identifying gaps that could be addressed through interventional clinical trials.

2. Major Methods and Findings ​

The review discusses various methodologies employed in ctDNA analysis, emphasizing their maturity and effectiveness as diagnostic tools. Key findings highlight that ctDNA can provide crucial information about tumor genetics, enabling oncologists to tailor treatments based on the molecular profile of tumors. The review also points out that accumulating clinical evidence supports the potential of ctDNA in early detection of cancer, tracking treatment responses, and monitoring for minimal residual disease. However, it notes that the full clinical potential of ctDNA remains to be thoroughly explored, especially through rigorous interventional clinical trials designed to assess its utility in diverse clinical scenarios.

3. Core Conclusions ​

The authors conclude that ctDNA liquid biopsy holds significant promise for revolutionizing cancer management. Its ability to provide real-time insights into tumor dynamics can enhance early detection and individualized treatment strategies. However, the review underscores the necessity of further research to validate ctDNA's effectiveness and to establish standardized protocols for its clinical application. The integration of ctDNA analysis into routine clinical practice could lead to more personalized and effective cancer care.

4. Research Significance and Impact ​

The significance of this research lies in its potential to transform oncology by shifting towards more precise and less invasive diagnostic methods. By focusing on ctDNA, oncologists may be able to improve patient outcomes through better monitoring and tailored therapies. The implications extend beyond individual patient care; as more data emerges from clinical trials, ctDNA could pave the way for new diagnostic paradigms and therapeutic strategies in oncology. This evolution in cancer management could ultimately lead to reduced healthcare costs and improved quality of life for patients, making ctDNA a critical area for future investigation and development in cancer research.

References ​

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  2. Biopsies: next-generation biospecimens for tailoring therapy. - Mark Basik;Adriana Aguilar-Mahecha;Caroline Rousseau;Zuanel Diaz;Sabine Tejpar;Alan Spatz;Celia M T Greenwood;Gerald Batist - Nature reviews. Clinical oncology (2013)
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Literatures Citing This Work ​

  1. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. - Anne Marie Lennon;Adam H Buchanan;Isaac Kinde;Andrew Warren;Ashley Honushefsky;Ariella T Cohain;David H Ledbetter;Fred Sanfilippo;Kathleen Sheridan;Dillenia Rosica;Christian S Adonizio;Hee Jung Hwang;Kamel Lahouel;Joshua D Cohen;Christopher Douville;Aalpen A Patel;Leonardo N Hagmann;David D Rolston;Nirav Malani;Shibin Zhou;Chetan Bettegowda;David L Diehl;Bobbi Urban;Christopher D Still;Lisa Kann;Julie I Woods;Zachary M Salvati;Joseph Vadakara;Rosemary Leeming;Prianka Bhattacharya;Carroll Walter;Alex Parker;Christoph Lengauer;Alison Klein;Cristian Tomasetti;Elliot K Fishman;Ralph H Hruban;Kenneth W Kinzler;Bert Vogelstein;Nickolas Papadopoulos - Science (New York, N.Y.) (2020)
  2. Bioactive DNA from extracellular vesicles and particles. - Ethan Z Malkin;Scott V Bratman - Cell death & disease (2020)
  3. Patient specific circulating tumor DNA fingerprints to monitor treatment response across multiple tumors. - Jiaping Li;Wei Jiang;Jinwang Wei;Jianwei Zhang;Linbo Cai;Minjie Luo;Zhan Wang;Wending Sun;Shengzhou Wang;Chen Wang;Chun Dai;Jun Liu;Guan Wang;Jiping Wang;Qiang Xu;Yanhong Deng - Journal of translational medicine (2020)
  4. Clonal Hematopoiesis in Liquid Biopsy: From Biological Noise to Valuable Clinical Implications. - Hiu Ting Chan;Yoon Ming Chin;Yusuke Nakamura;Siew-Kee Low - Cancers (2020)
  5. Non-Invasive Early Molecular Detection of Gastric Cancers. - Hiroyuki Yamamoto;Yoshiyuki Watanabe;Yoshinori Sato;Tadateru Maehata;Fumio Itoh - Cancers (2020)
  6. Biology-guided radiotherapy: redefining the role of radiotherapy in metastatic cancer. - Shervin M Shirvani;Calvin J Huntzinger;Thorsten Melcher;Peter D Olcott;Yevgen Voronenko;Judy Bartlett-Roberto;Samuel Mazin - The British journal of radiology (2021)
  7. The potential of using blood circular RNA as liquid biopsy biomarker for human diseases. - Guoxia Wen;Tong Zhou;Wanjun Gu - Protein & cell (2021)
  8. Peptide-Affinity Precipitation of Extracellular Vesicles and Cell-Free DNA Improves Sequencing Performance for the Detection of Pathogenic Mutations in Lung Cancer Patient Plasma. - Catherine Taylor;Simi Chacko;Michelle Davey;Jacynthe Lacroix;Alexander MacPherson;Nicholas Finn;Gabriel Wajnberg;Anirban Ghosh;Nicolas Crapoulet;Stephen M Lewis;Rodney J Ouellette - International journal of molecular sciences (2020)
  9. Longitudinal tumor fraction trajectories predict risk of progression in metastatic HR+ breast cancer patients undergoing CDK4/6 treatment. - Nadia Dandachi;Florian Posch;Ricarda Graf;Christoph Suppan;Eva Valentina Klocker;Hannah Deborah Müller;Jörg Lindenmann;Angelika Terbuch;Ellen Heitzer;Marija Balic - Molecular oncology (2021)
  10. Circulating Methylated DNA to Monitor the Dynamics of RAS Mutation Clearance in Plasma from Metastatic Colorectal Cancer Patients. - Chiara Nicolazzo;Ludovic Barault;Salvatore Caponnetto;Marco Macagno;Gianluigi De Renzi;Angela Gradilone;Francesca Belardinilli;Enrico Cortesi;Federica Di Nicolantonio;Paola Gazzaniga - Cancers (2020)

... (261 more literatures)

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