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Review
. 2023 Aug 29:1:100007.
doi: 10.1016/j.jlb.2023.100007. eCollection 2023 Sep.

Circulating tumor DNA in clinical trials for solid tumors: Challenges and current applications

Claudia Parisi  1   2 , Marco Tagliamento  3   4 , Laila Belcaid  5 , Mihaela Aldea  3   6 , Arnaud Bayle  1 , Jordi Remon-Masip  3 , Antoine Italiano  1   7 , David Planchard  3   6 , Benjamin Besse  3   6 , Fabrice Barlesi  3   6
Affiliations
Review

Circulating tumor DNA in clinical trials for solid tumors: Challenges and current applications

Claudia Parisi et al. J Liq Biopsy. .

Abstract

Tumor derived biomarkers including circulating tumor DNA (ctDNA) and/or circulating tumors cells (CTCs) may be detected and quantified through liquid biopsy (LB). ctDNA analysis through LB is a validated tool for monitoring response to systemic treatment and detecting molecular mechanisms of resistance at the time of progression of advanced stage malignancies. Several applications of ctDNA have been investigated in the diagnostic phase of cancer or in the post-curative treatment surveillance phase (e.g., minimal residual disease assessment after neoadjuvant or adjuvant therapy). Recently, the improvement of ctDNA technology and its implementation have affected early phase trials design, with significant changes in the inclusion and randomization phases. Implementation of LB has resulted in large-scale development of academic programs aimed at exploiting all the potential applications of ctDNA, such as patients extended molecular screening, molecular oriented treatment decision making, monitoring of anti-cancer treatments response. In this rapid evolving field, the challenge is no longer the technique, but the evaluation of the results and the interpretation of their impact on diagnosis, prognosis, or therapeutic decision. Leading research cancer centers may favor education for scientific community, by capturing data on this evolving technology and sharing knowledge. In this review we summarize the main applications and challenges of ctDNA genotyping in clinical trials, with special focus on ongoing studies. We finally describe the most important next generation academic and industry-sponsored programs addressing early cancer detection and prevention in high-risk populations through ctDNA genotyping.

Keywords: Cancer; Clinical trials; Early detection; Liquid biopsy; Minimal residual disease; Molecular genotyping; Molecular resistance; ctDNA.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
ctDNA from non-blood biological fluids as a potential alternative to plasma ctDNA.
See this image and copyright information in PMC

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