Liquid Biopsy Assay Enriches Tumor DNA for Early Detection and Monitoring

Circulating tumor-derived DNA (ctDNA) is often present at very low levels in plasma, making cancer detection and monitoring through liquid biopsy technically challenging. Background cell-free DNA from healthy cells can further obscure tumor signals, limiting assay sensitivity particularly in early-stage disease and minimal residual disease (MRD) surveillance. A new liquid biopsy method aims to overcome this limitation by generating plasma sequence datasets containing more than 99% cancer-derived DNA.

Capture-Seq from VolitionRx Limited is described in the first peer-reviewed paper on the approach, published in Clinical Epigenetics on July 21, 2026, under the title “Direct analysis of transcription factor protected cfDNA in plasma by ChIP-seq: measurement of altered CTCF binding in cancer is a novel biomarker for liquid biopsy.” The technology is designed to isolate and analyze pure ctDNA from blood samples. The company reports that the method has produced highly enriched cancer-associated plasma DNA sequence sets.

The workflow targets transcription factor-protected regions of plasma DNA using chromatin immunoprecipitation sequencing (ChIP-seq), focusing on fragments bound by CCCTC-binding factor (CTCF). The process combines physical enrichment with bioinformatic removal of nearly all remaining non-tumor cell-free DNA (cfDNA). Although the method captures only a subset of total ctDNA, the resulting sequence datasets are described as virtually pure cancer-derived DNA.

Initial results included two independent cohorts with no false positives. In the first, the method detected all 49 cancers, including 23 stage I/II cases, alongside 21 controls. In a second blinded cohort, it detected 13 of 14 later-stage cancers with 10 additional controls. Subsequent blinded validation in 81 subjects, including 59 patients with colorectal or lung cancer and 22 healthy controls, showed 95% detection among stage I/II cancers. The technology is being explored for multi-cancer early detection, minimal residual disease detection, and treatment monitoring, with further studies underway.

“From a clinical perspective, the proof of concept and early blinded validation results reported in this paper are extremely encouraging. In two independent cohorts we reported no false positives and detected 49/49 cancers in the first cohort (including 23 early-stage I/II and 21 controls) and validated it in a second blinded cohort with 13/14 later stage cancers detected with 10 additional controls. We have also subsequently reported data from a blinded validation cohort of 81 subjects (colorectal and lung cancer patients = 59, healthy controls = 22) and are extremely encouraged by the results; the early-stage cancer detection of 95% of stage I and II cancers is particularly noteworthy. For patients, the potential significance is huge,” said Dr Andrew Retter, medical consultant, Volition.

“If validated in larger cohorts, CTCF Capture-Seq could contribute to Multi-Cancer Early Detection (MCED) fulfilling a significant unmet clinical need. We also believe that Capture-Seq™ has the potential to play a role in cancer management, including but not limited to, Minimal Residual Disease detection and treatment monitoring, either alone or potentially in combination with other technologies too," added Dr. Retter.