Circulating Tumor DNA and Minimal Residual Disease (MRD) in Solid Tumors: Current Horizons and Future Perspectives
Open accessAbstract
Circulating tumor DNA (ctDNA) is cell-free DNA (cfDNA) fragment in the bloodstream that originates from malignant tumors or circulating tumor cells. Recently, ctDNA has emerged as a promising non-invasive biomarker in clinical oncology. Analysis of ctDNA opens up new avenues for individualized cancer diagnosis and therapy in various types of tumors. Evidence suggests that minimum residual disease (MRD) is closely associated with disease recurrence, thus identifying specific genetic and molecular alterations as novel MRD detection targets using ctDNA has been a research focus. MRD is considered a promising prognostic marker to identify individuals at increased risk of recurrence and who may benefit from treatment. This review summarizes the current knowledge of ctDNA and MRD in solid tumors, focusing on the potential clinical applications and challenges. We describe the current state of ctDNA detection methods and the milestones of ctDNA development and discuss how ctDNA analysis may be an alternative for tissue biopsy. Additionally, we evaluate the clinical utility of ctDNA analysis in solid tumors, such as recurrence risk assessment, monitoring response, and resistance mechanism analysis. MRD detection aids in assessing treatment response, patient prognosis, and risk of recurrence. Moreover, this review highlights current advancements in utilizing ctDNA to monitor the MRD of solid tumors such as lung cancer, breast cancer, and colon cancer. Overall, the clinical application of ctDNA-based MRD detection can assist clinical decision-making and improve patient outcomes in malignant tumors.
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Imaging may lack sensitivity for detecting early molecular relapse or minimal residual disease in pediatric sarcomas, particularly when tumor burden is low.
“While imaging plays an essential role in disease assessment, it may lack sensitivity for detecting early molecular relapse or minimal residual disease (MRD), particularly when tumor burden is low [9,10].”
From Circulating Tumor DNA and microRNA–Based Liquid Biopsy for Longitudinal Treatment Monitoring and Recurrence Prediction in Pediatric Sarcomas: A Prospective Cohort Study (2026) · cites this paper as [10]
The Other Tumors section reports that ctDNA detected tumors an average of 4.6 months before imaging and could identify MRD in advance, supporting the general point that imaging may miss early disease. The cited examples concern other solid tumors, not pediatric sarcomas, and the paper does not establish the imaging limitation specifically for that population or at low tumor burden. The statement about limited sensitivity at low ctDNA levels in Challenges and Future Directions concerns ctDNA assays, not imaging. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAcross early-stage solid tumors, postoperative or post-treatment ctDNA detection is consistently associated with a higher risk of recurrence.
“Across early-stage solid tumors, postoperative or post-treatment ctDNA detection is consistently associated with a higher risk of recurrence”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [10]
The clinical utility of ctDNA for directing treatment escalation or de-escalation in early-stage solid tumors remains under prospective evaluation.
“although its clinical utility for directing treatment escalation or de-escalation remains under prospective evaluation [ 9 , 10 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [10]
In early-stage solid tumors, ctDNA detection after curative-intent therapy has shown strong clinical validity for predicting future relapse.
“In early-stage solid tumors, ctDNA detection after curative-intent therapy has shown strong clinical validity for predicting future relapse”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [10]
Tumor-informed assays can improve sensitivity by tracking patient-specific alterations identified from tissue sequencing.
“Tumor-informed assays can improve sensitivity by tracking patient-specific alterations identified from tissue sequencing”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [10]
MRD detection requires substantially greater analytical sensitivity than baseline genotyping because tumor-derived DNA may be present at very low levels after surgery or definitive therapy.
“MRD detection is the most clinically ambitious use of ctDNA in sarcoma. It requires substantially greater analytical sensitivity than baseline genotyping because tumor-derived DNA may be present at very low levels after surgery or definitive therapy [ 5 , 9 , 10 , 11 , 12 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [10]
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References 106 · Cited by 167
- Authors
- Peng, Y., Mei, W., Ma, K., & Zeng, C.
- Affiliations
- Hubei University of Science and Technology (CN)
- Guangdong Medical College (CN)
- Corresponding author
- Zeng, Changchun
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2021-11-18
- Volume
- 11
- Pages
- 763790-763790
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC8637327
- OpenAlex
- W3217709761
- Cited by
- 167
- References
- 106
- Citations by year
- 2026: 31 · 2025: 36 · 2024: 41 · 2023: 40 · 2022: 19
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81660755)
- Science and Technology Planning Project of Shenzhen Municipality (JCYJ20170307160524377, JCYJ20190808162605484)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- circulating tumor DNA, minimal residual disease, cell-free DNA, solid tumors, liquid biopsy, non-invasive biomarkers, recurrence, treatment response monitoring, prognostic factors, lung cancer, breast cancer, colon cancer, resistance mechanisms
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