Oncoscience. 2026 Mar 5;13:44-54. doi: 10.18632/oncoscience.645. eCollection 2026.

ABSTRACT

BACKGROUND: High grade serous ovarian cancer (HGSOC) recurs frequently and commercial tests have emerged for tumor-informed, cell-free DNA (cfDNA)-based detection of minimal residual disease. These tests are based on somatic single nucleotide variants prevalent in many cancers and thus are not well matched to HGSOC, which is dominated by structural genomic rearrangements. The purpose of this study was to evaluate the feasibility of a structural-variant (SV)-informed, cfDNA-based method for detecting clonal and subclonal HGSOC disease burden.

METHODS: A method was developed for detecting patient-specific SV breakpoints using digital droplet PCR (ddPCR) with custom tumor-informed primer/probe pairs. Test parameters were first estimated using synthetic cfDNA generated by ultrasonication of genomic DNA from ovarian cancer cell lines. The optimized workflow was implemented in which whole genome sequencing of multisite pre-treatment HGSOC biopsies performed and high confidence SVs were called by multiple published SV callers. Real-time PCR and ddPCR were used for assay development.

RESULTS: Following the optimized workflow, tumor-specific SV breakpoint-spanning primers/probe sets of four HGSOC patients' multisite biopsies were designed and validated by real-time PCR and ddPCR. Together with four HGSOCs, a total of 29 SVs breakpoints-spanning tumor-informed primers/probe sets were designed and validated in multisite biopsies. 15 validated tumor-specific SVs were selected for quantification in their corresponding liquid biopsies using the validated ddPCR, and 9 had measurements in liquid biopsies.

CONCLUSIONS: Our result shows the detection of SVs from pre-treatment cfDNA using tumor-informed breakpoints-spanning ddPCR is feasible and may enable a novel and sensitive method for monitoring on-treatment disease burden.

PMID:41835357 | PMC:PMC12981705 | DOI:10.18632/oncoscience.645

Diagnostics (Basel). 2026 Feb 24;16(5):645. doi: 10.3390/diagnostics16050645.

ABSTRACT

Background/Objectives: Colorectal cancer (CRC) liver metastases present a significant clinical challenge due to high recurrence risks post-resection. Traditional diagnostics often fail to detect early-stage minimal residual disease (MRD). This preliminary pilot study evaluated ctDNA dynamics in 10 patients with liver metastases using a personalized multistep approach. Methods: Following primary tumor Next-Generation Sequencing (NGS) to identify somatic mutations in KRAS, NRAS, TP53, RET, APC, and WRN, custom TaqMan assays were designed for longitudinal plasma analysis. Four methodologies were compared: HRM-PCR, PNA-enhanced qPCR, and two digital platforms (dPCR and ddPCR). Results: While HRM-PCR sensitivity was limited in plasma, digital platforms demonstrated 100% qualitative concordance. MRD-negative status (VAF 0.00%) was identified in 70% of cases (P01, P03, P06, P07, P08, P09, P10), while detectable ctDNA in patients P02, P04, and P05 strongly correlated with aggressive progression. Digital PCR enabled the ultra-low detection of Variant Allele Frequencies (VAFs), identifying high molecular burdens (e.g., P05, VAF 49%) correlating with rapid decline, and capturing early molecular residue in P04 (VAF 0.62%). Conclusions: Our preliminary findings confirm that personalized longitudinal VAF tracking via digital PCR provides superior prognostic value, serving as a robust tool for recurrence monitoring in personalized CRC therapy.

PMID:41827921 | PMC:PMC12984390 | DOI:10.3390/diagnostics16050645

Cancers (Basel). 2026 Feb 28;18(5):800. doi: 10.3390/cancers18050800.

ABSTRACT

BACKGROUND AND OBJECTIVE: Liquid biopsy has transformed the management of advanced prostate cancer, yet its clinical role in non-metastatic disease remains uncertain. Conventional biomarkers such as PSA, imaging, and pathology have limited ability to capture minimal residual disease and biological aggressiveness. The objective of this review was to critically evaluate the current evidence on circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in non-metastatic prostate cancer, focusing on feasibility, prognostic value, and potential clinical applications.

METHODS: A narrative review of PubMed-indexed original studies evaluating liquid biopsy in clinically localized or non-metastatic prostate cancer was performed. Eligible studies included patients treated with curative-intent local therapy or experiencing biochemical recurrence without radiologic metastases. Study designs were predominantly prospective or retrospective observational cohorts. Liquid biopsy analytes included CTCs and ctDNA assessed from peripheral blood plasma using EpCAM-based enrichment, targeted next-generation sequencing, whole-genome sequencing, or ultra-sensitive tumor-informed assays. Primary outcomes included detection rates, associations with clinicopathologic features, biochemical recurrence, metastasis-free survival, and overall survival. Key Findings and Limitations: Across 11 studies, CTC detection using EpCAM-based platforms was infrequent in localized disease and biochemical recurrence and showed limited prognostic value (10-11% in preoperative settings). In contrast, ctDNA was detectable in a minority of patients but consistently identified biologically aggressive disease and a higher risk of recurrence when present, particularly using tumor-informed ultra-sensitive assays. Limitations include low detection rates, heterogeneous methodologies, small sample sizes, and predominantly exploratory study designs.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Currently, its most promising application is not broad screening, but as a selective, biology-driven tool for detecting minimal residual disease and refining risk assessment. CtDNA acts as a biological risk modifier, potentially guiding the escalation or de-escalation of adjuvant therapy. However, prospective biomarker-driven trials are required to validate these strategies before routine clinical implementation.

PMID:41827734 | PMC:PMC12984391 | DOI:10.3390/cancers18050800

Curr Opin Urol. 2026 Mar 6. doi: 10.1097/MOU.0000000000001387. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Personalised medicine has rapidly reshaped the management of urothelial carcinoma, driven by advances in tumour genomics, immune profiling and targeted drug development. This review is timely as multiple biomarker-driven therapies have recently entered routine clinical practice across disease stages, necessitating an integrated appraisal of how precision approaches should be applied and sequenced in contemporary care.

RECENT FINDINGS: Key advances include the expanding role of immune biomarkers beyond PD-L1, such as tumour mutational burden and DNA damage response alterations, to refine the use of immune checkpoint inhibitors. FGFR3 alterations represent the first validated genomic target in urothelial carcinoma, with FGFR inhibitors now established treatment options. Antibody-drug conjugates targeting Nectin-4 and HER2 have demonstrated substantial clinical activity, redefining treatment paradigms in both first-line and refractory settings. In parallel, circulating tumour DNA has emerged as a powerful dynamic biomarker for minimal residual disease detection and adjuvant treatment selection.

SUMMARY: Urothelial carcinoma has transitioned into a biomarker-driven disease, enabling more precise, biologically informed treatment decisions. Integrating genomic, immunologic and liquid biopsy biomarkers will be essential to optimise patient selection, treatment sequencing and toxicity management, and represents a critical direction for future research and clinical practice.

PMID:41827087 | DOI:10.1097/MOU.0000000000001387

J Thorac Dis. 2026 Feb 28;18(2):171. doi: 10.21037/jtd-2025-1-2467. Epub 2026 Feb 26.

ABSTRACT

BACKGROUND: Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare malignancies with limited treatment options and no established biomarkers for surveillance. Circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) provide a non-invasive method for understanding tumor biology, detecting minimal residual disease (MRD), and possibly identifying recurrence. While this approach has added to the management of other solid tumors, its role in TETs remains poorly defined. The objective of this review was to evaluate the feasibility, molecular insights, and clinical utility of cfDNA and ctDNA for diagnosis, molecular profiling, and recurrence monitoring in TETs.

METHODS: This systematic review summarizes the current evidence on cfDNA and ctDNA in TETs. Studies were identifies through systematic searches of PubMed, Embase, Web of Science, MEDLINE, Cochrane Library, and American Society of Clinical Oncology (ASCO) meeting abstracts from inception through July 2025. Eligible studies reported cfDNA or ctDNA analysis in patients with histologically confirmed thymoma or thymic carcinoma, and excluded reviews, commentaries, abstracts without full text, and non-blood based liquid biopsy studies. Data extraction included patient characteristics, assay platforms, mutational findings, and clinical applications. Data were synthesized narratively due to methodological heterogeneity. No formal risk of bias assessment was performed because of the small number of included studies.

RESULTS: Six studies involving 289 patients met inclusion criteria. ctDNA detection was feasible across all studies, with detection rates ranging from 46% to 80%. Recurrent alterations included TP53, CDKN2A/B, KIT, and other variants. Liquid biopsy enabled genomic profiling at diagnosis and dynamic monitoring during treatment. Notably, several studies have suggested that disease recurrence may be detectable through liquid biopsy prior to the appearance of radiographic changes on conventional imaging. Despite these promising observations, evidence remains limited by small sample size, variability in assay methods, and short follow up duration.

CONCLUSIONS: Liquid biopsy approaches based on cfDNA and ctDNA have shown applicability in TETs and provide clinically relevant molecular information in settings where tissue-based analysis is limited. Tumor informed ctDNA strategies show particular promise for postoperative monitoring and longitudinal disease assessment, whereas broader clinical adoption remains investigational. Further prospective, multicenter studies are needed to establish standardized workflows and clarify the role of liquid biopsy across diagnostic, therapeutic, and surveillance contexts in TETs.

PMID:41816481 | PMC:PMC12972770 | DOI:10.21037/jtd-2025-1-2467

Cancer Treat Rev. 2026 Mar;144:103111. doi: 10.1016/j.ctrv.2026.103111. Epub 2026 Feb 17.

ABSTRACT

Distant recurrence remains a significant cause of mortality in patients with breast cancer (BC). While metastasis was once considered a late event, current evidence suggests that metastatic seeding occurs early. There is thus significant interest in neoadjuvant therapy (NAT) as a window of opportunity to decrease metastatic risk. While NAT has classically consisted of chemotherapy, targeted therapies, such as human epidermal growth factor 2 (HER2)-targeted therapies and immune checkpoint inhibitors (ICIs), are now offered to patients with HER2-positive and triple-negative (TN) BC, respectively. As therapies evolve, there is a growing need to identify reliable biomarkers to predict NAT response and monitor microscopic disease post-NAT. This review explores the interplay between metastasis biomarkers and NAT for HER2-positive and TNBC. Circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), disseminated cancer cells (DCCs), and tumour-infiltrating lymphocytes (TILs) provide longitudinal insights into residual disease, immune dynamics, and genomic alterations. This review critically examines the established and emerging prognostic, predictive, and response-adaptive roles of these biomarkers in the neoadjuvant setting and beyond. Clinical adoption of novel biomarker approaches has been challenging due to reliance on tissue biopsy during an already challenging treatment journey. However, liquid biopsy approaches like CTC and ctDNA analyses provide minimally invasive means of monitoring metastatic risk. Technological advancements, such as methylome sequencing and variant-based ctDNA detection, offer promise for improved sensitivity and validity. While further trials are required to establish their clinical utility, integrating these biomarker-informed assays may inform precise metastasis risk assessment and improve patient outcomes.

PMID:41734562 | DOI:10.1016/j.ctrv.2026.103111