Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation

The detection of circulating tumor DNA (ctDNA) in liquid biopsy samples as an oncological marker is being used in clinical trials at every step of clinical management. As ctDNA-based liquid biopsy kits are developed and used in clinics, companies work towards increased convenience, accuracy, and cos...

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Main Authors: Jonathan Dao, Patrick J. Conway, Baskaran Subramani, Devi Meyyappan, Sammy Russell, Daruka Mahadevan
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/17/13219
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author Jonathan Dao
Patrick J. Conway
Baskaran Subramani
Devi Meyyappan
Sammy Russell
Daruka Mahadevan
author_facet Jonathan Dao
Patrick J. Conway
Baskaran Subramani
Devi Meyyappan
Sammy Russell
Daruka Mahadevan
author_sort Jonathan Dao
collection DOAJ
description The detection of circulating tumor DNA (ctDNA) in liquid biopsy samples as an oncological marker is being used in clinical trials at every step of clinical management. As ctDNA-based liquid biopsy kits are developed and used in clinics, companies work towards increased convenience, accuracy, and cost over solid biopsies and other oncological markers. The technology used to differentiate ctDNA and cell-free DNA (cfDNA) continues to improve with new tests and methodologies being able to detect down to mutant allele frequencies of 0.001% or 1/100,000 copies. Recognizing this development in technology, the FDA has recently given pre-market approval and breakthrough device designations to multiple companies. The purpose of this review is to look at the utility of measuring total cfDNA, techniques used to differentiate ctDNA from cfDNA, and the utility of different ctDNA-based liquid biopsy kits using relevant articles from PubMed, clinicaltrials.gov, FDA approvals, and company newsletters. Measuring total cfDNA could be a cost-effective, viable prognostic marker, but various factors do not favor it as a monitoring tool during chemotherapy. While there may be a place in the clinic for measuring total cfDNA in the future, the lack of standardization means that it is difficult to move forward with large-scale clinical validation studies currently. While the detection of ctDNA has promising standardized liquid biopsy kits from various companies with large clinical trials ongoing, their applications in screening and minimal residual disease can suffer from lower sensitivity. However, researchers are working towards solutions to these issues with innovations in technology, multi-omics, and sampling. With great promise, further research is needed before liquid biopsies can be recommended for everyday clinical management.
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spelling doaj.art-1c6ad2996fab449586e4c4c2088ac84f2023-11-19T08:14:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171321910.3390/ijms241713219Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical ValidationJonathan Dao0Patrick J. Conway1Baskaran Subramani2Devi Meyyappan3Sammy Russell4Daruka Mahadevan5Long School of Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USAMays Cancer Center, University of Texas Health, San Antonio, TX 78229, USAMays Cancer Center, University of Texas Health, San Antonio, TX 78229, USAMays Cancer Center, University of Texas Health, San Antonio, TX 78229, USALong School of Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USALong School of Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USAThe detection of circulating tumor DNA (ctDNA) in liquid biopsy samples as an oncological marker is being used in clinical trials at every step of clinical management. As ctDNA-based liquid biopsy kits are developed and used in clinics, companies work towards increased convenience, accuracy, and cost over solid biopsies and other oncological markers. The technology used to differentiate ctDNA and cell-free DNA (cfDNA) continues to improve with new tests and methodologies being able to detect down to mutant allele frequencies of 0.001% or 1/100,000 copies. Recognizing this development in technology, the FDA has recently given pre-market approval and breakthrough device designations to multiple companies. The purpose of this review is to look at the utility of measuring total cfDNA, techniques used to differentiate ctDNA from cfDNA, and the utility of different ctDNA-based liquid biopsy kits using relevant articles from PubMed, clinicaltrials.gov, FDA approvals, and company newsletters. Measuring total cfDNA could be a cost-effective, viable prognostic marker, but various factors do not favor it as a monitoring tool during chemotherapy. While there may be a place in the clinic for measuring total cfDNA in the future, the lack of standardization means that it is difficult to move forward with large-scale clinical validation studies currently. While the detection of ctDNA has promising standardized liquid biopsy kits from various companies with large clinical trials ongoing, their applications in screening and minimal residual disease can suffer from lower sensitivity. However, researchers are working towards solutions to these issues with innovations in technology, multi-omics, and sampling. With great promise, further research is needed before liquid biopsies can be recommended for everyday clinical management.https://www.mdpi.com/1422-0067/24/17/13219liquid biopsycfDNActDNA
spellingShingle Jonathan Dao
Patrick J. Conway
Baskaran Subramani
Devi Meyyappan
Sammy Russell
Daruka Mahadevan
Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation
International Journal of Molecular Sciences
liquid biopsy
cfDNA
ctDNA
title Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation
title_full Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation
title_fullStr Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation
title_full_unstemmed Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation
title_short Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation
title_sort using cfdna and ctdna as oncologic markers a path to clinical validation
topic liquid biopsy
cfDNA
ctDNA
url https://www.mdpi.com/1422-0067/24/17/13219
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