Front Oncol. 2026 Aug 28;16:1907210. doi: 10.3389/fonc.2026.1907210. eCollection 2026.

ABSTRACT

Clonal evolution in hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), and gastric cancer (GC) reflects the interaction of genetic diversification, cell-state plasticity, and tissue-specific selection. Multi-region and single-cell DNA sequencing resolve truncal and subclonal lineages, whereas single-cell and spatial transcriptomics, proteomics, and serial liquid biopsy characterize cellular states, ecological niches, and temporal dynamics. The three cancers differ in dissemination timing, dominant selective pressures, and biomarker maturity: early seeding is best supported in selected HCC cohorts, ESCC is strongly influenced by field cancerization and epithelial-stromal crosstalk, and GC follows subtype- and ecotype-dependent trajectories. We discuss the assumptions and sampling biases that constrain phylogenetic inference, the causal limits of cross-sectional tumor atlases, clonal hematopoiesis, and the incremental value of broad multi-omics over focused assays. Liquid-biopsy detection of minimal residual disease is prognostic, but treatment benefit from marker-guided intervention remains context dependent. Near-term translation requires standardized, decision-linked assays; adaptive therapy and evolutionary steering remain investigational.

PMID:42729528 | PMC:PMC13563159 | DOI:10.3389/fonc.2026.1907210

Open Res Eur. 2026 Apr 3;6:87. doi: 10.12688/openreseurope.23403.1. eCollection 2026.

ABSTRACT

BACKGROUND: Pancreatic cancer and ovarian cancer are very challenging to diagnose at early stages. The endoscopic retrieval of biopsy tissue from a suspected benign or malignant lesion is challenging due to the tissue's nature. Therefore, within the Instand-NGS4P framework, we developed Measurable Residual Disease (MRD) prototypes to analyze blood plasma samples, with the aim of cost-effectively supporting the differential diagnosis of suspected pancreatic or ovarian neoplasms.

METHODS: Our MRD prototypes examine blood plasma for mutations in cell-free DNA in specific genes associated with pancreatic neoplasms or ovarian neoplasms, respectively. Unique molecular identifiers (UMIs) are used to enable bioinformatic error correction. Ultra-deep sequencing is demonstrated on sequencing platforms from two different vendors (Illumina and MGI). We provide detailed information on bioinformatic processing of sequencing data to perform error-correction.

RESULTS: Using commercially available reference standards, we demonstrate stable mutation detection down to a variant allele frequency (VAF) of 0.1%. At a coverage of 4,000x duplex consensus reads, only two false positives were observed, which can be efficiently mitigated using an appropriate filtering strategy.

CONCLUSIONS: The technical usability of our MRD prototype has been clearly demonstrated for stable low-level VAF detection in commercial reference samples.

PMID:42728989 | PMC:PMC13560845 | DOI:10.12688/openreseurope.23403.1

J Mol Diagn. 2026 Sep 11:S1525-1578(26)00156-X. doi: 10.1016/j.jmoldx.2026.08.002. Online ahead of print.

ABSTRACT

Analysis of circulating tumor-DNA (ctDNA) provides a molecular assessment that can complement routine imaging in childhood cancer management. Detailed monitoring of ctDNA levels may provide information on treatment efficacy and resistance, minimal residual disease and allows for early detection of relapse. Here, tumor-informed ctDNA analysis was applied to 90 blood plasma samples collected from eight children with malignant tumors. Four to ten tumor-specific mutations per patient were assessed using SiMSen-Seq, a digital sequencing approach utilizing unique molecular identifiers (UMIs). The effects of individual SiMSen-Seq assays and plasma samples were evaluated in relation to their impact on background error rate, number of detected target molecules and mutant calling using different UMI family size cutoff settings. The use of at least two sequencing reads per UMI provided the best overall performance by generating the highest number of detected target molecules and hence the optimal chance to detect low-frequent mutations. Data were consistent between SiMSen-Seq assays and plasma samples, providing robust ctDNA profiling over time for all patients. In conclusion, the results show that optimal use of UMIs in tumor-informed ctDNA analysis enables sensitive molecular readout that can assist in management of childhood cancers.

PMID:42727690 | DOI:10.1016/j.jmoldx.2026.08.002

Endokrynol Pol. 2026 Sep 11. doi: 10.5603/ep.112817. Online ahead of print.

ABSTRACT

The incidence of thyroid cancer has increased dramatically over the past four decades, making it the most common endocrine malignancy worldwide. Although well-differentiated thyroid carcinomas generally exhibit excellent survival rates following standard surgical and radioactive iodine interventions, the clinical management of high-risk variants, recurrent disease, and indeterminate nodules remains a significant challenge. Historically, the evaluation of thyroid nodules has relied on B-mode ultrasonography and fine-needle aspiration biopsy (FNAB). However, spatial and temporal tumor heterogeneity, coupled with the high rate of indeterminate cytology (Bethesda Categories III and IV), often leads to unnecessary diagnostic thyroidectomies. In recent years, liquid biopsy has emerged as a promising diagnostic approach, offering a non-invasive, dynamic, and comprehensive method for disease monitoring. This comprehensive review evaluates the biological mechanisms and clinical utility of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), and non-coding RNAs in thyroid oncology. Furthermore, it explores the clinical role of commercial molecular diagnostic panels (e.g., Afirma GSC, ThyroSeq v3) in guiding surgical decisions. This review highlights the diagnostic synergy achieved when these molecular biomarkers are integrated with advanced radiological modalities - including strain elastography, quantitative region-of-interest (ROI) analysis, ACR TI-RADS, and cross-sectional volumetric tracking - as well as nuclear medicine techniques like technetium-99m MIBI scintigraphy. Emerging applications of artificial intelligence and radiomics in image analysis, alongside the concept of minimal residual disease monitoring, are also discussed. Ultimately, we emphasize the need for a multidisciplinary team (MDT) approach in translating these multi-omics and multimodal imaging data into precision medicine, while acknowledging current limitations and charting future directions.

PMID:42725427 | DOI:10.5603/ep.112817

Front Oncol. 2026 Aug 27;16:1919279. doi: 10.3389/fonc.2026.1919279. eCollection 2026.

ABSTRACT

Lung Cancer (LC) continues to be the biggest cause of cancer-related deaths around the world, mostly because of delayed diagnosis. Even if tissue biopsies and circulating tumor DNA (ctDNA) tests have revolutionized clinical management of LC patients, their effectiveness is restricted in settings with lower tumor burden, molecular heterogeneity, and bias in sampling approaches. In this scenario, the epigenetic profiling of cell-free DNA (cfDNA) stands out as a promising, less invasive approach, accurately detect cancer traces. Evidence from stage I-II disease and CT-detected pulmonary nodules supports the diagnostic potential of cfDNA methylation, although further validation in prospective screening cohorts remains necessary. Beyond genomic alterations, cfDNA epigenetic changes, including DNA methylation, chromatin organization, nucleosome positioning, and fragmentation patterns, reflect multi-dimensional complexity of tumor biology. These properties convey both the functional status and the origin of the circulating DNA fragments, accelerating for tumor integrating genomic analysis. Within this group, DNA methylation is the biologically robust and clinically well-established epigenetic marker, as alterations in methylation linked to cancer often occur in the early stages of tumorigenesis and are commonly found across different cancer cell types. Here, we explored the biological and clinical relevance of the epigenetic landscape of cfDNA in LC patients, particularly focusing on DNA methylation-based biomarkers and their evolving applications towards early diagnosis and post-surgical monitoring of minimal residual disease (MRD). We aimed to comprehensively overview analytical approaches for cfDNA methylation analysis, including targeted and genome-wide profiling strategies, and discuss their integration with machine learning (ML) and multi-omics frameworks in order to improve diagnostic performance and clinical applicability in LC management.

PMID:42724581 | PMC:PMC13559918 | DOI:10.3389/fonc.2026.1919279

Front Oncol. 2026 Aug 26;16:1909934. doi: 10.3389/fonc.2026.1909934. eCollection 2026.

ABSTRACT

Circulating tumor DNA (ctDNA), a core component of liquid biopsy, demonstrates significant potential in the field of neoadjuvant therapy for solid tumors. This review systematically examines the role of ctDNA across the pre-, intra-, and post-neoadjuvant treatment phases, with a focus on its value in predicting therapeutic efficacy, assessing early treatment response, detecting minimal residual disease (MRD), and monitoring for recurrence. By synthesizing the latest clinical research data and advancements in molecular detection technologies, this article aims to elucidate how ctDNA is facilitating a shift towards more precise, dynamic, and individualized paradigms in neoadjuvant therapy for solid tumors. Furthermore, it analyzes the current challenges and future directions for integrating ctDNA analysis into clinical practice to optimize patient management and outcomes. Throughout, clinically validated applications are explicitly distinguished from those that remain investigational, and key unresolved questions are highlighted.

PMID:42719676 | PMC:PMC13555526 | DOI:10.3389/fonc.2026.1909934

Breast Cancer (Auckl). 2026 Sep 3;20:11782234261485831. doi: 10.1177/11782234261485831. eCollection 2026.

ABSTRACT

Breast cancer remains the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women worldwide, underscoring the need for accurate, minimally invasive biomarkers to support precision oncology. Conventional tissue biopsy remains the standard for molecular characterization but is limited by its invasiveness, inability to capture spatial and temporal tumor heterogeneity, and challenges in serial monitoring. Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA, has emerged as a promising liquid biopsy biomarker capable of providing real-time genomic information throughout disease progression. This narrative review examines recent advances in ctDNA biology, analytical technologies, clinical applications, current limitations, and future directions in breast cancer management. A structured literature search of PubMed/MEDLINE, Scopus, Embase, Web of Science, and Google Scholar identified relevant English-language publications from 2015 to 2026. Current evidence indicates that highly sensitive platforms, including digital PCR, BEAMing, and next-generation sequencing, can detect clinically actionable alterations in genes such as PIK3CA, ESR1, TP53, ERBB2, AKT1, and BRCA1/2. ctDNA has demonstrated particular utility in identifying minimal residual disease, monitoring therapeutic response, detecting emerging resistance mechanisms, and guiding targeted treatment selection in advanced breast cancer. However, applications in early cancer detection, population screening, and artificial intelligence-assisted clinical decision-making remain investigational. Widespread clinical implementation is constrained by low ctDNA abundance in early-stage disease, analytical variability, limited assay standardization, and cost considerations. Continued technological innovation, prospective multicenter validation, standardized testing protocols, and evidence-based clinical guidelines are essential to fully integrate ctDNA into routine precision breast cancer care.

PMID:42699009 | PMC:PMC13542536 | DOI:10.1177/11782234261485831

Ther Adv Urol. 2026 Sep 2;18:17562872261485770. doi: 10.1177/17562872261485770. eCollection 2026 Jan-Dec.

ABSTRACT

High-risk non-muscle invasive bladder cancer poses therapeutic challenges, with significant rates of recurrence and progression with standard intravesical bacillus Calmette-Guérin (BCG) therapy. Current surveillance strategies lack accurate risk stratification models to predict individual treatment response and personalized treatment options. Simultaneously, there are no well-validated alternatives to replace the current gold-standard approach based on clinical and pathologic features. This review examines emerging biomarkers and advanced technologies with the potential to enhance patient selection and personalize intravesical therapy in HR-NMIBC. Artificial intelligence(AI)-driven histopathologic tools, such as the computer histological AI biomarker, have demonstrated the ability to identify non-responders to standard therapy using whole-slide digital pathology images. In parallel, radiomics-enhanced imaging has shown promise in assessing tumor biology and immune microenvironment features predictive of BCG responsiveness. Liquid biopsy, especially urine tumor DNA analysis, is now available in the arsenal to detect minimal residual disease, stratify recurrence risk, and predict treatment response even before clinical or radiographic evidence of recurrence. Tissue-based genomic profiling has also revealed molecular alterations associated with treatment resistance, though additional validation is needed. Together, these next-generation biomarkers may represent a pivotal shift toward precision oncology in bladder cancer and their incorporation into NMIBC future clinical guidelines is both anticipated and necessary.

PMID:42694519 | PMC:PMC13539006 | DOI:10.1177/17562872261485770

Front Immunol. 2026 Aug 20;17:1934257. doi: 10.3389/fimmu.2026.1934257. eCollection 2026.

ABSTRACT

The therapeutic landscape of multiple myeloma (MM) has undergone a profound transformation, with highly effective combination regimens and immune-based therapies enabling unprecedented rates of deep and durable responses. As a result, conventional baseline risk stratification alone is increasingly insufficient to explain the heterogeneity of clinical outcomes or to guide treatment throughout the disease course. This evolving paradigm has shifted attention toward dynamic, response-adapted disease monitoring centered on measurable residual disease (MRD) and the biological interaction between residual tumor cells and the host immune system. Bone marrow-based next-generation flow cytometry and next-generation sequencing currently represent the most extensively validated approaches for MRD assessment, while functional imaging, mass spectrometry, circulating tumor DNA, and other minimally invasive technologies are expanding the ability to monitor spatially heterogeneous disease and longitudinal clonal evolution. Although sustained MRD negativity has emerged as one of the most powerful prognostic biomarkers in MM, its clinical significance is influenced by multiple factors, including timing of assessment, sensitivity, durability of response, baseline disease biology, imaging findings, and the quality of immune reconstitution. Increasing evidence indicates that relapse following MRD negativity reflects not only residual tumor burden below the limits of detection but also a dynamic biological process driven by clonal evolution, microenvironmental protection, immune escape, and therapeutic selection pressure. Immune profiling provides complementary information by characterizing immune competence, including T-cell and natural killer-cell function, immune reconstitution after therapy, regulatory and myeloid immunosuppressive networks, and the immune fitness required for effective T-cell redirection and the capacity to sustain effective antitumor immune surveillance. Integrating longitudinal MRD kinetics with immune biomarkers has the potential to improve risk discrimination, identify biologically discordant disease states, and support rational strategies for treatment intensification, de-escalation, or discontinuation within prospective clinical trials. In the era of anti-CD38 antibodies, CAR T-cell therapy, bispecific antibodies, and emerging multi-antigen immunotherapies, disease monitoring is evolving beyond the assessment of tumor burden alone. Future of MM management will likely rely on multidimensional monitoring frameworks that integrate MRD, immune competence, spatial disease assessment, circulating biomarkers, and computational risk modeling to enable truly personalized, biology-driven patient care.

PMID:42694447 | PMC:PMC13539482 | DOI:10.3389/fimmu.2026.1934257

ESMO Gastrointest Oncol. 2026 Aug 25;13(Pt B):100407. doi: 10.1016/j.esmogo.2026.100407. eCollection 2026 Sep.

ABSTRACT

BACKGROUND: Despite advances in perioperative and neoadjuvant strategies, patients with locally advanced gastroesophageal cancers remain at high risk of recurrence after curative intent treatment. No validated biomarkers are available to detect minimal residual disease (MRD) or to guide post-operative risk-adapted management. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool for disease monitoring; single-parameter or tumor-informed assays, however, may lack sensitivity in low-tumor burden settings. Multimodal, tumor-agnostic approaches may overcome these limitations.

METHODS: The BUTTERFLY study is a prospective, multicenter observational study enrolling patients with stage II-III gastric, gastroesophageal junction, or esophageal cancer treated with perioperative chemotherapy or neoadjuvant chemoradiotherapy followed by surgery. It evaluates the diagnostic performance and prognostic value of an academic, tumor-agnostic, multimodal ctDNA assay for MRD detection and prognostic stratification. Serial plasma samples are collected from baseline through post-operative follow-up and at relapse. Cell-free DNA is analyzed using the Agnostic Liquid Biopsy Multimodal Advancement (ALMA) platform, integrating tumor fraction estimation, somatic copy number alterations, fragmentomic features, single-nucleotide variants, and whole-genome methylation profiling. Multimodal features are combined with clinical variables using machine learning-based models to enhance MRD detection and relapse risk stratification. The primary endpoint includes sensitivity and specificity of ALMA-defined ctDNA/MRD status at the 4-8 weeks after surgery landmark, whereas secondary endpoints assess diagnostic performance at other time points and associations between ctDNA status and dynamics with disease-free survival, overall survival, treatment response, and lead time to recurrence.

FUTURE PERSPECTIVES: If validated, this tumor-agnostic, multimodal ctDNA approach may enable earlier molecular relapse detection and support personalized post-operative management strategies.

PMID:42688382 | PMC:PMC13534848 | DOI:10.1016/j.esmogo.2026.100407

J Liq Biopsy. 2026 Aug 18;13:100487. doi: 10.1016/j.jlb.2026.100487. eCollection 2026 Sep.

ABSTRACT

Circulating tumor DNA (ctDNA) has demonstrated utility for treatment monitoring, risk stratification, and prognostication in colorectal cancer (CRC). However, substantial methodological heterogeneity across studies may influence its reported prognostic performance. Here, we systematically searched four databases up to October 2025. Eligible studies included patients with CRC who underwent mutation-based plasma ctDNA analysis reported as a binary variable (positive/negative) and provided hazard ratios (HRs) with 95% confidence intervals (95%CIs) for recurrence-free survival (RFS), disease-free survival (DFS), progression-free survival (PFS), or overall survival (OS). Pooled HRs were synthesized using random-effects meta-analysis. Thirty-seven studies met the inclusion criteria. ctDNA positivity was consistently associated with inferior outcomes across all survival endpoints, including OS (HR 3.52; 95%CI 2.42-5.13; p < 0.001; I² = 74.4%), RFS (HR 4.90; 95%CI 3.54-6.79; p < 0.001; I² = 83.5%), DFS (HR 4.41; 95%CI 2.96-6.55; p < 0.001; I² = 84.7%), and PFS (HR 2.46; 95%CI 1.88-3.21; p < 0.001; I² = 39.2%). The prognostic value of ctDNA was greatest in localized (stage I-III) disease, where it most likely reflects minimal residual disease (MRD). Post-treatment ctDNA demonstrated substantially greater prognostic value than baseline ctDNA, supporting its role in MRD assessment. Persistent ctDNA positivity following surgery and adjuvant chemotherapy identified patients at the highest risk of recurrence and death. Methodological factors were associated with differences in reported prognostic performance: tumor-informed assays outperformed tumor-agnostic assays, particularly in localized disease, while NGS-based approaches showed stronger prognostic performance than dPCR or qPCR. In conclusion, ctDNA positivity is strongly associated with adverse survival outcomes across CRC stages and clinical settings, supporting its role as a clinically relevant biomarker. However, methodological variability significantly influences the reported magnitude of this association, underscoring the need for standardized protocols and transparent reporting to facilitate comparison across studies and support reliable clinical implementation of ctDNA-guided management.

PMID:42668443 | PMC:PMC13524542 | DOI:10.1016/j.jlb.2026.100487

Ther Adv Urol. 2026 Aug 27;18:17562872261481954. doi: 10.1177/17562872261481954. eCollection 2026 Jan-Dec.

ABSTRACT

Muscle-invasive bladder cancer (MIBC) remains associated with high recurrence and mortality despite radical cystectomy and cisplatin-based neoadjuvant chemotherapy (NAC). For decades, perioperative therapy was defined by platinum-based regimens, which improve survival but are limited to fewer than half of patients due to comorbidities. Recent advances in the past year have redefined this landscape. Multiple pivotal phase III trials have demonstrated the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings. The phase III trials, KEYNOTE-905/EV-303 and KEYNOTE-B15/EV-304 have established perioperative enfortumab vedotin plus pembrolizumab as a new standard of care for neoadjuvant therapy. Parallel translational research has identified biomarkers that may refine patient selection and optimize therapy. PD-L1 expression, DNA damage repair gene alterations, molecular subtyping, and circulating tumor DNA (ctDNA) have all emerged as predictive and prognostic tools. Liquid biopsy approaches may guide adjuvant therapy decisions and facilitate real-time monitoring of minimal residual disease. This review synthesizes the evolving role of perioperative therapies in MIBC, from the historical reliance on cisplatin-based chemotherapy to the transformative integration of immunotherapy, ADCs, and biomarker-guided approaches. Together, these advances represent a significant progress in perioperative bladder cancer care, heralding a shift toward individualized, biomarker-driven strategies that promise improved survival and broader treatment applicability.

PMID:42666617 | PMC:PMC13522676 | DOI:10.1177/17562872261481954

Front Oncol. 2026 Jul 30;16:1901721. doi: 10.3389/fonc.2026.1901721. eCollection 2026.

ABSTRACT

BACKGROUND: Circulating tumor DNA (ctDNA) is being studied for prognosis and treatment monitoring in pancreatic ductal adenocarcinoma (PDAC). Given the limitations of CA19-9, including non-secretion and confounding by cholestasis, we assessed whether serial ctDNA dynamics predict progression-free survival (PFS) and overall survival (OS) in localized and advanced PDAC, and whether ctDNA adds information to CA19-9.

METHODS: We conducted a PRISMA-guided systematic review of PubMed, Translational Research, MDPI, and JAMA. Eligible studies included patients with PDAC who had ≥2 ctDNA measurements during perioperative care, treatment, or surveillance and reported associations with OS, PFS, DFS/RFS, recurrence, progression, EMR, molecular progression, or lead-time versus imaging/CA19-9. Two reviewers screened 119 records, of which 17 studies met inclusion criteria. Because of heterogeneity in assays, sampling schedules, and reporting, results were synthesized narratively.

RESULTS: Across studies, ctDNA detectability and clinical utility varied according to disease stage, assay type, and sampling window. In resected PDAC, a CLIA-validated ddPCR KRAS assay study reported preoperative ctDNA detection in 49% of patients (29/59). In the same cohort, ctDNA detected during follow-up predicted recurrence with 90% sensitivity (95% CI, 74%-98%) and 88% specificity (95% CI, 62%-98%) and preceded clinical or radiographic recurrence by a median of 84 days (IQR, 25-146). In advanced PDAC treated with palliative chemotherapy, longitudinal sampling every 4 weeks showed that ctDNA monitoring identified progression before radiology in 20 of 30 patients (67%) with baseline-detectable ctDNA, with a median lead time of 23 days (P = 0.01). In the same cohort, CA19-9 increases, when present, showed a shorter median lead time of 9.5 days (P = 0.03), and ctDNA detected progression in some patients without a corresponding CA19-9 increase during therapy. Across the included studies, baseline ctDNA positivity was generally associated with higher-risk disease, whereas early ctDNA decline or clearance during treatment and postoperative or longitudinal ctDNA negativity were associated with more favorable outcomes.

CONCLUSION: Serial ctDNA dynamics in PDAC were associated with recurrence, progression, treatment response, and survival across perioperative and systemic therapy settings. ctDNA appears most consistent as a postoperative MRD marker and may complement CA19-9 and imaging during treatment monitoring. Prospective studies are needed to standardize sampling schedules, response thresholds, and ctDNA-guided clinical use.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261321972, identifier CRD420261321972.

PMID:42657157 | PMC:PMC13508053 | DOI:10.3389/fonc.2026.1901721

Front Oncol. 2026 Aug 12;16:1955091. doi: 10.3389/fonc.2026.1955091. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fonc.2026.1901721.].

PMID:42656868 | PMC:PMC13508048 | DOI:10.3389/fonc.2026.1955091

Int J Mol Sci. 2026 Aug 10;27(16):7155. doi: 10.3390/ijms27167155.

ABSTRACT

Endometrial and cervical cancers can recur from subclinical disease not evident on routine surveillance. This narrative review critically evaluates liquid biopsy for minimal residual disease (MRD) assessment and recurrence monitoring. Post-treatment human papillomavirus (HPV) circulating tumor DNA (ctDNA) in cervical cancer has the strongest disease-specific prospective evidence of clinical validity; persistent detection is strongly associated with recurrence, but moderate sensitivity and false-negative results do not support treatment de-escalation on negativity alone. With regard to endometrial cancer, perioperative ctDNA has prognostic support from an 11-study, 1298-patient meta-analysis and additional cohorts, although assay heterogeneity and limited independent replication constrain clinical readiness. Postoperative positivity generally shows stronger associations than preoperative detection. Cervicovaginal and urine DNA-methylation studies provide preliminary evidence for detecting established recurrence, especially local recurrence, but not prospective molecular lead time or clinical utility. Digital PCR, disease-specific fixed panels, tumor-informed assays, and error-corrected sequencing serve distinct settings; broad pan-cancer plasma profiling remains mainly an advanced-disease tool. Circulating tumor cells, extracellular vesicles, microRNAs, tumor-educated platelets, and fragmentomics remain exploratory. Liquid biopsy should remain an investigational adjunct until prospective trials show that acting on molecular findings improves outcomes.

PMID:42653160 | PMC:PMC13513691 | DOI:10.3390/ijms27167155

J Clin Med. 2026 Aug 11;15(16):6222. doi: 10.3390/jcm15166222.

ABSTRACT

Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker for detecting minimal residual disease (MRD) and predicting recurrence after curative treatment, yet evidence in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cancer has largely been examined within individual tumor types. In this scoping review, we mapped this evidence across all three malignancies and clarified key methodological and clinical considerations. Following the PRISMA-ScR guidelines, we searched PubMed, Scopus, and the Cochrane Library (3 April 2026) for studies linking ctDNA to disease-free, recurrence-free, or overall survival after curative-intent treatment. Twenty-seven studies (1746 patients; 10 ESCC, 4 EAC, 8 gastric, and 5 mixed) were included. Across every tumor type, postoperative ctDNA MRD was the most informative timepoint, with independent multivariable hazard ratios for disease-free, recurrence-free, or event-free survival of 2.8 to 21.8, whereas preoperative ctDNA was seldom prognostic. Serial monitoring further improved performance and flagged recurrence 78 to 278 days before imaging. Tumor-informed assays showed higher sensitivity than tumor-agnostic ones (80% vs. 35%), though direct comparisons were limited; correction for clonal hematopoiesis was essential for tumor-agnostic assays, and blood-based assays performed poorly in diffuse-type and peritoneal disease. Postoperative ctDNA MRD is a consistent, independent prognostic biomarker across upper gastrointestinal cancers that adds prognostic information beyond conventional staging and pathological response, supporting prospective interventional trials of ctDNA-guided management.

PMID:42652626 | PMC:PMC13513700 | DOI:10.3390/jcm15166222

Clin Chim Acta. 2026 Aug 25;593:121299. doi: 10.1016/j.cca.2026.121299. Online ahead of print.

ABSTRACT

Acute lymphoblastic leukemia (ALL) represents the most common malignancy diagnosed in children, accounting for approximately 25-30% of all pediatric cancers. Despite remarkable improvements in survival rates over recent decades, with cure rates exceeding 90% in developed countries, the diagnosis and monitoring of ALL continue to rely on invasive bone marrow aspiration and morphological assessment. MicroRNAs (miRNAs), small non-coding RNA molecules that regulate gene expression post-transcriptionally, have emerged as promising biomarkers for cancer diagnosis and prognosis due to their stability in biological fluids, tissue-specific expression patterns, and regulatory roles in oncogenesis. This comprehensive review systematically examines the current evidence regarding miRNA expression profiles in pediatric ALL, focusing on their diagnostic potential, prognostic value, and applicability as non-invasive biomarkers. Aberrant miRNA expression has been consistently demonstrated in pediatric ALL, with specific signatures distinguishing B-cell precursor ALL from T-cell ALL, identifying cytogenetic subtypes, and predicting treatment response. Circulating miRNAs, particularly those packaged within exosomes, offer non-invasive alternatives for minimal residual disease monitoring and early relapse detection. Machine learning approaches integrating multi-miRNA panels have achieved high diagnostic accuracy, with several miRNAs, including miR-128-3p, miR-181a, miR-196b, miR-200c, and miR-326, demonstrating significant clinical utility. MicroRNA profiling represents a transformative approach to pediatric ALL management, offering enhanced diagnostic precision, improved risk stratification, and non-invasive monitoring capabilities. While challenges remain in standardizing detection methodologies and establishing clinically validated thresholds, the integration of miRNA biomarkers into clinical practice holds substantial promise for personalized medicine in childhood leukemia.

PMID:42641935 | DOI:10.1016/j.cca.2026.121299

Front Oncol. 2026 Aug 10;16:1806868. doi: 10.3389/fonc.2026.1806868. eCollection 2026.

ABSTRACT

Therapy resistance remains a leading cause of treatment failure and mortality in thoracic malignancies, despite major advances in targeted therapies and immunotherapies. Resistance evolves through heterogeneous, patient-specific mechanisms, including genetic alterations, epigenetic reprogramming, lineage plasticity, and tumor-microenvironment interactions, often emerging before radiographic progression or clinical relapse. Conventional tissue biopsies and imaging, while essential for diagnosis and treatment selection, are limited in their ability to capture spatial and temporal tumor heterogeneity or to support dynamic monitoring of tumor evolution. Liquid biopsy has therefore emerged as a minimally invasive approach for real-time assessment of tumor-derived biomarkers in circulation, enabling longitudinal tracking of resistance biology across the cancer care continuum. In this review, we highlight recent advances in liquid biopsy applications for thoracic malignancies, focusing on circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) as complementary analytes for baseline molecular profiling, detection of primary and acquired resistance to therapy, and identification of minimal residual disease and molecular relapse. Beyond mutation-based approaches, we highlight emerging non-genomic ctDNA features, including epigenomic and fragmentomic signatures, that capture treatment-induced adaptation and lineage plasticity not detectable by conventional plasma genomic profiling, and discuss advances in CTC technologies that preserve cellular and phenotypic context relevant to resistance and metastatic potential. Finally, we examine multimodal liquid biopsy strategies that integrate multiple circulating analytes with artificial intelligence-assisted methods to enhance sensitivity, provide a more comprehensive view of tumor biology, and inform adaptive therapy strategies. We also outline key analytical and clinical challenges that must be addressed through standardized, prospective trials to translate liquid biopsy-guided surveillance and early interception of resistance into improved patient outcomes.

PMID:42639369 | PMC:PMC13501364 | DOI:10.3389/fonc.2026.1806868

Biosci Rep. 2026 Sep 16;46(9):BSR20250409. doi: 10.1042/BSR20250409.

ABSTRACT

Ovarian cancer remains one of the deadliest gynecological malignancies, mainly due to its late diagnosis, biological heterogeneity, and frequent development of chemoresistance. Recent evidence indicates that epigenetic dysregulation including aberrant DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA networks plays an important role in the initiation, progression, and therapeutic response of ovarian cancer. Unlike genetic alterations, epigenetic modifications are reversible, making them attractive targets for drug development and precision oncology. In this review, we provide a detailed overview of the epigenetic mechanisms that control ovarian cancer biology, with specific focus on their role in drug resistance and disease recurrence. We discuss the role of epigenetic plasticity in enabling transition of tumor cells into drug tolerant, stem like phenotypes, leading to minimal residual disease and eventual relapse without permanent genetic changes. Attention is given to the influence of DNA methyltransferases, histone deacetylases, enhancer of zeste homolog 2, and chromatin remodeling complexes in the maintenance of adaptive resistance programs. We also discuss the evolving paradigm of epigenetic regulation, immune modulation and viral mimicry and provide the rationale for combining epigenetic therapies with immunotherapy and poly(ADP-ribose) polymerase inhibition. The article also reviews the results of recent clinical trials and evaluate the most recent advances in biomarker development, such as circulating DNA methylation signatures, microRNAs, and artificial intelligence-based liquid biopsy platforms. Finally, we discussed the potential implications of applying epigenetic profiling in the clinic for improved patient stratification and the potential for real-time monitoring of chemoresistance. These progresses make epigenetic regulation a promising strategy to overcome chemoresistance and improve personalized medicine of ovarian cancer.

PMID:42638590 | PMC:PMC13507039 | DOI:10.1042/BSR20250409

Curr Oncol Rep. 2026 Aug 24;28(1):85. doi: 10.1007/s11912-026-01816-0.

ABSTRACT

PURPOSE OF REVIEW: Recurrence following curative-intent treatment for head and neck squamous cell carcinoma (HNSCC) approaches 50% in locally advanced disease, yet conventional surveillance detects relapse only after anatomical or metabolic thresholds are reached. Minimal residual disease (MRD) monitoring, using circulating tumor DNA (ctDNA) and viral DNA biomarkers, offers an earlier, molecularly informed framework for post-treatment surveillance. This structured narrative review synthesizes contemporary evidence on MRD in HNSCC, drawing on a search of PubMed and Scopus covering January 2020 to March 2026, and defines its role as a clinical instrument for risk-adapted surveillance and decision-making.

RECENT FINDINGS: Across prospective cohorts and platform-validation studies, MRD positivity is independently associated with recurrence risk, with hazard ratios ranging from 3- to tenfold across tumor-informed ctDNA platforms, and molecular relapse frequently precedes radiologic detection by months. Viral DNA assays demonstrate specificities exceeding 95% in virally mediated subtypes. Early interventional data suggest potential for MRD-guided treatment adaptation, but results have been mixed: a recent HPV ctDNA-guided de-escalation trial closed early due to an unacceptable recurrence rate, underscoring that standardized thresholds, optimal testing intervals, and definitive evidence of clinical utility remain unresolved. MRD should currently be integrated as an adjunct to established surveillance modalities rather than a standalone trigger for intervention. Results are best interpreted longitudinally, and an early post-treatment molecular checkpoint at 2-6 weeks represents a high-yield decision point where confirmed positivity may justify intensified evaluation and multidisciplinary review.

PMID:42635847 | DOI:10.1007/s11912-026-01816-0