Curated Papers > High-Impact Authoritative Literature on "Liquid Biopsy"

Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer.

Literature Information

DOI	10.18632/oncotarget.9453
PMID	27223063
Journal	Oncotarget
Publication Year	2016
Times Cited	197
Keywords	biology, biomarker, circulating tumor DNA, liquid biopsy, targeted therapies
Literature Type	Journal Article, Review
ISSN	1949-2553
Pages	48832-48841
Issue	7(30)
Authors	Feifei Cheng, Li Su, Cheng Qian

TL;DR

This paper reviews the potential of circulating tumor DNA (ctDNA) as a revolutionary approach for cancer diagnosis and management, highlighting its advantages over traditional tissue biopsies, which are limited by tumor heterogeneity. The findings suggest that ctDNA analysis not only enhances the sensitivity and specificity of genetic mutation screening but also improves tumor monitoring, prognosis, and the efficacy of targeted therapies, thereby facilitating early-stage cancer detection.

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biology · biomarker · circulating tumor DNA · liquid biopsy · targeted therapies

Abstract

Tissue biopsy is the standard diagnostic procedure for cancers and also provides a material for genotyping, which can assist in the targeted therapies of cancers. However, tissue biopsy-based cancer diagnostic procedures have limitations in their assessment of cancer development, prognosis and genotyping, due to tumor heterogeneity and evolution. Circulating tumor DNA (ctDNA) is single- or double-stranded DNA released by the tumor cells into the blood and it thus harbors the mutations of the original tumor. In recent years, liquid biopsy based on ctDNA analysis has shed a new light on the molecular diagnosis and monitoring of cancer. Studies found that the screening of genetic mutations using ctDNA is highly sensitive and specific, suggesting that ctDNA analysis may significantly improve current systems of tumor diagnosis, even facilitating early-stage detection. Moreover, ctDNA analysis is capable of accurately determining the tumor progression, prognosis and assisting in targeted therapy. Therefore, using ctDNA as a liquid biopsy may herald a revolution for tumor management. Herein, we review the biology of ctDNA, its detection methods and potential applications in tumor diagnosis, treatment and prognosis.

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Primary Questions Addressed

1. What are the current limitations of tissue biopsy that ctDNA analysis aims to address?
2. How does ctDNA analysis compare to traditional methods in terms of sensitivity and specificity for detecting genetic mutations?
3. What are the potential implications of using ctDNA for early-stage cancer detection on patient outcomes?
4. In what ways can ctDNA analysis assist in the personalization of targeted therapies for cancer patients?
5. What are the challenges in the standardization of ctDNA detection methods across different cancer types?

Key Findings

Research Background and Purpose

Tissue biopsy has traditionally been the gold standard for cancer diagnosis, providing critical material for genotyping and guiding targeted therapies. However, tissue biopsies have significant limitations, including challenges in assessing tumor heterogeneity, evolution, and early-stage detection. Circulating tumor DNA (ctDNA), which is released by tumor cells into the bloodstream, has emerged as a promising non-invasive biomarker for cancer diagnosis, monitoring, and treatment. This review aims to explore the biology of ctDNA, its detection methods, and its potential applications in oncology.

Main Methods/Materials/Experimental Design

The review discusses various methods for detecting ctDNA, emphasizing the advances in technology that enhance sensitivity and specificity. Key detection methods include:

1. Sanger Sequencing: Traditional method but limited by low throughput and high costs.
2. Next-Generation Sequencing (NGS): Provides high sensitivity and can detect low levels of ctDNA.
3. BEAMing: A technique that uses beads and flow cytometry to detect ctDNA.
4. CAPP-seq: A method targeting specific mutations for quantifying ctDNA.

The following flowchart summarizes the detection methodologies:

Key Results and Findings

• ctDNA Characteristics: ctDNA is associated with specific mutations found in tumors and reflects tumor burden more accurately than traditional biomarkers. Its half-life is less than 2 hours, allowing real-time monitoring of tumor dynamics.
• Clinical Applications: Studies have shown that ctDNA can significantly improve sensitivity in cancer detection compared to conventional markers. For example, ctDNA detection rates in metastatic breast cancer reached 97%, surpassing traditional biomarkers.
• Monitoring and Prognosis: ctDNA levels correlate with tumor stages and can predict relapse earlier than conventional methods, providing valuable insights into treatment efficacy and tumor evolution.

Main Conclusions/Significance/Innovation

The review highlights the potential of ctDNA as a revolutionary tool in cancer management, offering non-invasive, real-time insights into tumor dynamics, which could significantly enhance early detection, prognosis, and treatment personalization. The ability to monitor genetic mutations over time makes ctDNA a crucial element in the development of precision medicine.

Research Limitations and Future Directions

Despite its promise, the application of ctDNA in clinical practice faces challenges, including:

• Sensitivity Issues: Current detection methods may not always detect ctDNA in early-stage cancers.
• Understanding ctDNA Biology: More research is needed to clarify the biological characteristics of ctDNA, such as its fragment size and release mechanisms.
• Cost and Accessibility: The high costs of advanced sequencing technologies limit widespread clinical use.

Future research should focus on improving the sensitivity of detection methods, enhancing our understanding of ctDNA biology, and validating its clinical utility to ensure its integration into routine cancer care.

References

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Literatures Citing This Work

1. Integrating precision cancer medicine into healthcare-policy, practice, and research challenges. - Gabrielle Bertier;Jian Carrot-Zhang;Vassilis Ragoussis;Yann Joly - Genome medicine (2016)
2. Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring. - David Pérez-Callejo;Atocha Romero;Mariano Provencio;María Torrente - Translational lung cancer research (2016)
3. Diagnostic and prognostic value of circulating tumor DNA in gastric cancer: a meta-analysis. - Yunhe Gao;Kecheng Zhang;Hongqing Xi;Aizhen Cai;Xiaosong Wu;Jianxin Cui;Jiyang Li;Zhi Qiao;Bo Wei;Lin Chen - Oncotarget (2017)
4. Liquid biopsies in bladder cancer-did we find the Holy Grail for biomarker analyses? - Michael Rink;Shahrokh F Shariat;Armin Soave - Translational andrology and urology (2016)
5. Circulating Cell Free Tumor DNA Detection as a Routine Tool forLung Cancer Patient Management. - Julie A Vendrell;Frédéric Tran Mau-Them;Benoît Béganton;Sylvain Godreuil;Peter Coopman;Jérôme Solassol - International journal of molecular sciences (2017)
6. Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer. - Keigo Yokoi;Keishi Yamashita;Masahiko Watanabe - International journal of molecular sciences (2017)
7. Circulating Tumor DNA as Biomarkers for Cancer Detection. - Xiao Han;Junyun Wang;Yingli Sun - Genomics, proteomics & bioinformatics (2017)
8. Liquid biopsy: a step forward towards precision medicine in urologic malignancies. - Ashley Di Meo;Jenni Bartlett;Yufeng Cheng;Maria D Pasic;George M Yousef - Molecular cancer (2017)
9. Pattern recognition for predictive, preventive, and personalized medicine in cancer. - Tingting Cheng;Xianquan Zhan - The EPMA journal (2017)
10. The Role of BEAMing and Digital PCR for Multiplexed Analysis in Molecular Oncology in the Era of Next-Generation Sequencing. - Jérôme Alexandre Denis;Erell Guillerm;Florence Coulet;Annette K Larsen;Jean-Marc Lacorte - Molecular diagnosis & therapy (2017)

... (187 more literatures)

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