J Thorac Dis. 2026 Apr 30;18(4):415. doi: 10.21037/jtd-2026-1-0025. Epub 2026 Apr 24.

ABSTRACT

BACKGROUND AND OBJECTIVE: Circulating tumor cells (CTCs) are malignant cells shed into blood that enable noninvasive, longitudinal assessment of lung cancer. Increasing evidence frames CTCs within a circulating tumor microenvironment (cTME) and broader circulating tumor-associated cell (CTAC) ecosystems that include multicellular clusters and circulating tumor endothelial cells (CTECs). We summarize definitions, detection approaches, and clinical applications of CTC-centered liquid biopsy in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

METHODS: A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Google Scholar using the terms "non-small cell lung cancer", "small cell lung cancer", and "circulating tumor cells". Relevant clinical, basic, and translational studies were selected and synthesized to outline current knowledge and future directions.

KEY CONTENT AND FINDINGS: CTCs can be enriched by immunoaffinity, size, or microfluidic platforms, enabling enumeration and downstream profiling. In both NSCLC and SCLC, CTC positivity and higher burden are associated with worse survival, with the strongest effects in SCLC and with circulating tumor emboli (CTE). Serial monitoring provides early signals of response or failure; and post-treatment supports minimal residual disease (MRD) detection and relapse prediction. Molecular and phenotypic profiling enables driver and resistance tracking, including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), while CTECs may add vascular and immune-relevant information.

CONCLUSIONS: CTC-based assays have the potential to complement imaging and tissue biopsy across screening research, prognostication, therapeutic monitoring, MRD assessment, and personalized care. Clinical translation requires standardized preanalytical workflows, harmonized thresholds, and prospective trials testing CTC-guided management.

PMID:42182710 | PMC:PMC13190041 | DOI:10.21037/jtd-2026-1-0025

Int J Gen Med. 2026 May 18;19:602509. doi: 10.2147/IJGM.S602509. eCollection 2026.

ABSTRACT

Thyroid cancer (TC), the most prevalent endocrine malignancy worldwide, encompasses a broad spectrum of biological behaviors ranging from indolent microcarcinomas to lethal anaplastic variants. Despite advancements in standard care, critical clinical "bottlenecks" persist, including the diagnostic ambiguity of Bethesda III/IV nodules, the rising prevalence of radioiodine-refractory (RAI-R) differentiated TC, and the dismal survival rates of anaplastic thyroid carcinoma (ATC). The rapid evolution of biomarkers has catalyzed a paradigm shift from traditional anatomical-pathological staging to a sophisticated "Molecular Taxonomy" model, providing the cornerstone for precision oncology. This review systematically delineates the multi-dimensional landscape of TC biomarkers, encompassing genomic and transcriptomic drivers (eg, BRAF, RAS, TERT, RET, NTRK), epigenetic regulators (miRNAs, lncRNAs, circRNAs, and DNA methylation), and the proteomic interface. We highlight the transformative role of Liquid Biopsy 2.0-including ctDNA-based minimal residual disease (MRD) detection and exosomal multi-omics-in enabling non-invasive, longitudinal surveillance. Furthermore, we explore how cutting-edge technologies, such as single-cell sequencing and spatial transcriptomics, are deciphering intratumoral heterogeneity and redefining the "functional invasive front". Clinical translation is addressed through the lens of personalized management: from the use of genomic classifiers (eg, ThyroSeq v3) in preoperative triage to biomarker-guided "de-escalation" or "intensification" of therapy. Finally, we discuss the imperative of addressing ancestry-specific molecular divergence (specifically in Asian cohorts). However, significant challenges remain, including the high cost of multi-omics integration and the lack of standardized protocols for clinical implementation. We conclude by envisioning a future integrated with multimodal AI models, patient-derived organoids (PDOs), and metabolic reprogramming markers, aiming to provide a holistic framework for the "early screening-precise diagnosis-tailored therapy-dynamic monitoring" continuum in thyroid oncology.

PMID:42179850 | PMC:PMC13196814 | DOI:10.2147/IJGM.S602509

Curr Oncol Rep. 2026 May 23;28(1):59. doi: 10.1007/s11912-026-01799-y.

ABSTRACT

PURPOSE OF REVIEW: Liquid biopsy has emerged as a minimally invasive approach to overcome the limitations of tissue biopsy in oncology. This review aims to synthesize recent advances in its clinical applications, particularly in early cancer detection, therapeutic monitoring, and minimal residual disease (MRD), while discussing current challenges, regulatory perspectives, and future directions.

RECENT FINDINGS: Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles, and epigenetic markers are the most extensively studied biomarkers, in which clinical trials such as TRACERx and DYNAMIC have demonstrated that ctDNA monitoring enables earlier detection of recurrence and guides adjuvant therapy decisions more precisely than standard imaging. Commercially validated assays, including Guardant360 CDx, FoundationOne Liquid CDx, and Epi proColon, have received regulatory approval, reflecting growing clinical adoption; however, limitations persist, including reduced sensitivity in low-tumor burden settings, technical variability between platforms, and the risk of false positives from clonal hematopoiesis. Ongoing research highlights the promise of multi-omic approaches and the integration of artificial intelligence to improve sensitivity, capture tumor heterogeneity, and provide predictive insights into treatment response and resistance. Liquid biopsy represents a paradigm shift in precision oncology by enabling real-time, longitudinal tumor profiling. Although significant barriers remain, such as cost, accessibility, and lack of standardization, technological innovations and large-scale validation studies are paving the way for its routine clinical integration.

PMID:42176138 | DOI:10.1007/s11912-026-01799-y

Transl Lung Cancer Res. 2026 Apr 30;15(4):105. doi: 10.21037/tlcr-2025-aw-1321. Epub 2026 Mar 20.

ABSTRACT

BACKGROUND AND OBJECTIVE: Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Tissue biopsies are invasive and often limited, emphasizing the need for minimally invasive biomarkers. Circulating tumor DNA (ctDNA) obtained through liquid biopsy enables non-invasive tumor profiling. While most applications rely on mutation detection, DNA methylation of ctDNA (Met-ctDNA) represents a promising complementary approach. This review explores technological methods for detecting ctDNA methylation and summarizes its potential clinical applications in NSCLC.

METHODS: We analyzed recent studies describing methylation detection technologies, including polymerase chain reaction (PCR)-based, sequencing, microarray, and enrichment approaches. We also reviewed evidence on diagnostic, prognostic, and predictive applications of Met-ctDNA, as well as its role in monitoring minimal residual disease (MRD).

KEY CONTENT AND FINDINGS: Technically, sodium bisulfite conversion remains the gold standard, but new bisulfite-free and ultrasensitive strategies are emerging. Clinically, gene-specific hypermethylation (e.g., SHOX2, RASSF1A, and APC) provides high diagnostic specificity. Prognostic studies consistently link methylation markers and scores to overall and progression-free survival. Dynamic methylation changes predict response to chemotherapy, immunotherapy, and targeted therapy, especially in patients without actionable mutations. Moreover, Met-ctDNA enables earlier detection of MRD and recurrence than imaging, improving personalized follow-up. However, variability in sample processing, assay performance, and marker specificity remain significant barriers. Confounding factors such as age-related methylation variability, environmentally and lifestyle-induced methylation changes, and clonal hematopoiesis must also be considered when selecting relevant markers and interpreting results.

CONCLUSIONS: Met-ctDNA is a versatile, non-invasive biomarker with diagnostic, prognostic, and predictive value in NSCLC. Standardization of methodologies and validation in large-scale prospective trials are essential to enable its integration into routine clinical practice.

PMID:42170273 | PMC:PMC13186644 | DOI:10.21037/tlcr-2025-aw-1321

Adv Cancer Res. 2026;170:139-173. doi: 10.1016/bs.acr.2025.12.002. Epub 2025 Dec 16.

ABSTRACT

One of the most difficult global health issues is cancer, whose incidence and mortality rates are expected to rise significantly over the next several decades. This increasing burden highlights the need for early diagnosis, accurate prognostic tools, and predictive markers for individualized treatment plans. Biomarkers, which are measurable indicators of disease states or therapeutic responses, have become essential to modern oncology and are driving the precision medicine revolution by improving patient stratification, directing therapy choices, and facilitating disease monitoring. This review explores the development of cancer biomarkers, tracing their progression from early histopathological and serum markers to advanced molecular and immunological tools. The key biomarker categories discussed include genomic alterations such as somatic mutations, gene fusions, and copy number variations, all of which offer actionable insights for targeted therapies. Epigenetic markers, which include noncoding RNAs, histone modifications, and DNA methylation, are notable for their regulatory functions and hold promise as noninvasive diagnostic instruments. Proteomic and metabolomic methods offer useful insights into tumor biology, while circulating biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes, allow real-time, noninvasive monitoring of disease progression and minimal residual disease. Immunological biomarkers such as the tumor mutational burden (TMB) and programmed cell death ligand-1 (PD-L1) expression are becoming increasingly important in guiding immunotherapy choices. This study also highlights how emerging technologies, including next-generation sequencing, liquid biopsy platforms, and artificial intelligence-based analytics, have accelerated biomarker discovery and integration into clinical workflows. The observable advantages of biomarker-driven care are demonstrated by case studies and real-world applications in a variety of cancer types. Despite tremendous advancements, obstacles such as tumor heterogeneity, intertest variability, high costs, inconsistent regulations, and differences in healthcare infrastructure prevent widespread adoption, particularly in low- and middle-income nations where access to biomarker technologies is still unequal and could exacerbate global disparities in cancer outcomes. Future directions include the use of multiplex biomarker panels, the integration of digital pathology, and the exploration of novel biomarker domains such as the tumor microenvironment and microbiome. Personalized neoantigen-based vaccines and immunotherapies also represent promising frontiers. Overall, this review underscores the transformative potential of biomarkers in reshaping cancer diagnostics and therapeutics and calls for sustained collaborative research, technological advancements, and equitable policy frameworks to realize their full global impact.

PMID:42167838 | DOI:10.1016/bs.acr.2025.12.002

Clin Chim Acta. 2026 May 20;590:121103. doi: 10.1016/j.cca.2026.121103. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor (incidence 0.7-2.0 per million per year) with a 5-year survival rate of less than 15% at the European Network for the Study of Adrenal Tumors stage IV. The standard diagnostic workup in clinical chemistry laboratories for the detection of functional tumors (serum cortisol, DHEAS, and 24 h urinary free cortisol) and the Weiss/Helsinki histological scoring system cannot detect non-functioning tumors, lacks a standardized approach for predicting prognosis, and does not have a validated minimal-residual-disease marker for postoperative monitoring. This narrative review evaluated 246 original research publications on four multi-omic layers in relation to clinical laboratories. Genomic and transcriptomic analyses, including TCGA-ACC pan-genomic profiling, revealed recurrent driver mutations and prognostic molecular subtypes that outperform the ENSAT staging. Tissue and circulating proteomic analyses identified HNRNPA1, KPNA2, SOAT1, and plasma AgRP as diagnostic and pharmacoproteomic targets. Urinary and serum steroid metabolomics (GC-MS and liquid chromatography-tandem mass spectrometry) validated in a 2017-patient prospective EURINE-ACT cohort provided clinically actionable diagnostic accuracy of over 85% and proved informative for post-surgical recurrence monitoring. Multi-omics classification consistently identifies two distinct biologically based subtypes with therapeutic implications. We also discuss the pre-analytical, analytical, and inter-laboratory standardization requirements that must be met before each biomarker layer can be translated to the clinical chemistry laboratory and advocate a multi-omic implementation strategy for ACC diagnosis, prognosis, and recurrence detection.

PMID:42167637 | DOI:10.1016/j.cca.2026.121103

Folia Microbiol (Praha). 2026 May 21. doi: 10.1007/s12223-026-01503-4. Online ahead of print.

ABSTRACT

Human papillomavirus (HPV)-related cancers represent a significant and growing global health burden, encompassing cervical, anogenital, and an increasing proportion of head and neck squamous cell carcinomas, particularly oropharyngeal cancer. While tissue biopsy remains the cornerstone of diagnosis and initial molecular characterization, its invasive nature and inability to capture tumor heterogeneity or dynamic molecular changes limit its utility for longitudinal disease monitoring. Liquid biopsy has emerged as a powerful, minimally invasive approach that enables real-time assessment of tumor- and virus-derived biomarkers from blood, saliva, and other body fluids. Among these, circulating tumor HPV DNA (ctHPV-DNA) has demonstrated exceptional specificity and sensitivity, in HPV-driven malignancies, where viral DNA serves as a highly tumor-specific marker. Advances in analytical platforms, including droplet digital PCR and next-generation sequencing, have markedly improved the detection of low-abundance circulating biomarkers, enabling applications ranging from early detection and treatment response monitoring to minimal residual disease assessment and early identification of recurrence. This review provides a comprehensive overview of the current landscape of liquid biopsy in HPV-related cancers.

PMID:42165979 | DOI:10.1007/s12223-026-01503-4

Pathologie (Heidelb). 2026 May 21. doi: 10.1007/s00292-026-01568-5. Online ahead of print.

ABSTRACT

Molecular pathological tumor diagnostics are becoming increasingly important in the context of personalized medicine. Modern high-throughput methods now enable routine molecular tumor profiling to identify genetic aberrations. Tissue biopsies are firmly established in routine clinical practice and remain the gold standard for initial diagnosis and are generally a prerequisite for tumor resection. They provide essential histological and immunohistochemical information; however, obtaining them can sometimes be difficult or involve risks and is often limited by the availability of tumor material. Furthermore, due to intratumoral heterogeneity, the entire spectrum of mutations is not always captured, which can influence the selection of targeted therapies. Against this backdrop, liquid biopsy is gaining importance as a minimally invasive, complementary approach. It enables the analysis of tumor-associated genetic alterations in circulating tumor DNA (ctDNA) and allows for repeated and systemic detection of molecular changes. For selected clinical questions, ctDNA analysis is already established in routine clinical practice, particularly for the identification of predictive markers and the detection of therapy-associated resistance mechanisms, for example in non-small cell lung cancer (NSCLC) or breast cancer. However, its widespread application is limited by methodological challenges, primarily due to the low amount of ctDNA and the resulting high demands on sensitivity and specificity. This is particularly true for early detection, which remains the subject of intensive research and controversial discussions. ctDNA-based therapy monitoring and the detection of minimal residual disease (MRD) represent promising approaches but require further prospective studies for standardization and integration into clinical guidelines. This review summarizes the possibilities, limitations, and available methods as well as current and potential applications of liquid biopsy in molecular diagnostics.

PMID:42165849 | DOI:10.1007/s00292-026-01568-5

NPJ Breast Cancer. 2026 May 20. doi: 10.1038/s41523-026-00970-9. Online ahead of print.

ABSTRACT

Early detection of minimal residual disease (MRD) by liquid biopsy could enable earlier relapse identification in early-stage breast cancer (BC), but most approaches are single-analyte. We prospectively studied 58 patients with early-stage BC, including HR+/HER2-, triple-negative, and HER2+ subtypes, treated with neoadjuvant chemotherapy or primary surgery plus adjuvant therapy. Patient-specific droplet digital PCR assays were designed for both ctDNA and CTCs analysis, with one truncal tumour mutation tracked per patient for detection in both analytes, in serial high-volume blood samples collected at diagnosis before treatment, approximately 1 month after surgery, and at 6-month intervals during follow-up in patients at high risk of relapse. We developed a composite Liquid biopsy Minimal Residual Disease (L-MRD) score integrating six clinical and molecular variables. At baseline (pre-treatment), ctDNA and/or CTCs were detected in 67.2% of patients and remained positive post-surgery in 53.6%. During follow-up, MRD detection anticipated all relapses (100% sensitivity; median lead time 27.95 months) and the L-MRD score stratified 5-year recurrence risk (2.2% vs 41.6%; HR = 6.6; P = 0.04) with strong performance (AUC = 0.891; NPV = 97.8%). This dual-analyte, longitudinal MRD strategy improves relapse prediction and supports further research regarding the clinical utility of personalised surveillance in early-stage BC.

PMID:42161983 | DOI:10.1038/s41523-026-00970-9

Biosens Bioelectron. 2026 May 15;309:118809. doi: 10.1016/j.bios.2026.118809. Online ahead of print.

ABSTRACT

Tumor-derived exosomes carry multidimensional molecular cargo, including surface proteins, microRNAs, and lipids that encode tumor identity and disease dynamics. These features support their application as biomarkers for liquid biopsy-based cancer diagnostics. Circulating tumor DNA undergoes rapid nuclease-mediated degradation, whereas exosomes retain stable molecular information that reflects the proteomic, transcriptomic, and metabolic states of parent tumor cells. However, clinical translation of exosome-based sensing remains limited by variability in isolation, biological heterogeneity, and the analytical difficulty of detecting low-abundance biomarkers in clinical samples. In this review, we examine cancer-specific exosomal signatures across breast, lung, colorectal, and gastric cancers and evaluate biosensing platforms for exosomal biomarker profiling. We integrate engineering principles, clinical performance metrics, and AI-assisted analysis across complementary biosensing modalities to establish a cross-platform analytical framework. We compare optical platforms based on surface plasmon resonance, localized surface plasmon resonance, and surface-enhanced Raman scattering with photoluminescence- and electrochemical-based platforms in terms of sensitivity, clinical compatibility, and translational potential. Furthermore, we examine artificial intelligence (AI)-assisted biosensing frameworks, including classical machine learning classifiers, deep convolutional networks, ensemble models, explainable AI methods, and large language model interfaces. We evaluate how each framework addresses high-dimensional spectral complexity, nonlinear relationships among signals, and inter-patient variability in exosomal data. Finally, we identify remaining challenges, such as the lack of standardized isolation protocols and the absence of large-scale clinical validation. We further highlight minimal residual disease monitoring and early-stage cancer detection as important and underexplored directions for AI-integrated exosomal biosensing in precision oncology.

PMID:42161118 | DOI:10.1016/j.bios.2026.118809

J Gastroenterol Hepatol. 2026 May 18. doi: 10.1111/jgh.70420. Online ahead of print.

ABSTRACT

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with outcomes critically dependent on timely diagnosis, accurate risk stratification, and individualized treatment. Traditional markers such as CEA, KRAS/NRAS, BRAF, and MSI status, while foundational, are insufficient to address the full complexity of CRC biology. Over the past decade, a new generation of biomarkers has emerged spanning liquid biopsy, stool-based methylation, genomics, epigenomics, immune profiling, microbiome analysis, radiomics, patient-derived organoids, and multiomics integration-collectively redefining how CRC is detected, classified, and treated. This narrative review synthesizes evidence from 73 human studies published between 2010 and 2024, identified through structured searches of PubMed, Embase, Web of Science, and the Cochrane Library, and quality-assessed using QUADAS-2 and Newcastle-Ottawa tools. Circulating tumor DNA (ctDNA) emerged as the most clinically validated biomarker, demonstrating superior performance in minimal residual disease (MRD) detection, recurrence prediction, and real-time therapy monitoring. Stool DNA methylation assays showed strong sensitivity for early CRC and advanced adenoma detection. Genomic markers including BRAF V600E, POLE/POLD1, HER2, and KRAS G12C now directly inform targeted therapy selection, while immune biomarkers-MSI-H, TMB, and Immunoscore-guide immunotherapy decisions and stratify prognosis beyond TNM staging. Microbiome signatures, particularly Fusobacterium nucleatum and colibactin-producing Escherichia coli, were associated with chemo resistance and tumor progression. Radiomics and AI-driven imaging models provided noninvasive assessment of nodal involvement and neo-adjuvant therapy response. Patient-derived organoids demonstrated capacity to predict individual drug sensitivity, and multiomic integration enabled refined molecular subtyping. Despite this progress, widespread clinical adoption remains limited by assay variability, lack of prospective multicenter validation, and implementation barriers including cost and infrastructure. As these technologies mature, their integration into standardized, multidisciplinary workflows will be essential to translating biomarker innovation into improved patient outcomes across all stages of CRC care.

PMID:42150752 | DOI:10.1111/jgh.70420

Pharmacol Res. 2026 May 17:108253. doi: 10.1016/j.phrs.2026.108253. Online ahead of print.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) exemplifies early systemic dissemination, with circulating tumor cells (CTCs) at its core. We advance a unified conceptual framework that positions CTCs as the systemic execution hub of PDAC metastasis, dynamic entity that coordinates the metastatic cascade via four cardinal functions: Seeding, Adapting, Engineering, and Signaling. Integrating eco-evolutionary dynamics, this hub actively drives phenotypic selection, niche remodeling, and immune evasion, while providing real-time biologic intelligence through liquid biopsy. Robust clinical correlation has not yet translated into routine practice because of technical variability, biological complexity, and a lack of interventional evidence. We therefore propose an evidence-driven, phased roadmap: grounded in prospective clinical cohort data, progressing from immediate multi-center technical standardization and pragmatic trials, such as minimal residual disease (MRD)-triggered salvage therapy, to mid-term biomarker-driven adjuvant trials and long-term integration into multimodal liquid biopsy ecosystems, aimed at intercepting this execution hub. By reframing CTCs from correlative indicators to actionable therapeutic targets and dynamic sentinels, this framework charts a path toward transforming the management of this recalcitrant systemic disease.

PMID:42150733 | DOI:10.1016/j.phrs.2026.108253

Chin Clin Oncol. 2026 Apr;15(2):38. doi: 10.21037/cco-2025-aw-135.

ABSTRACT

BACKGROUND AND OBJECTIVE: Hepatopancreatobiliary (HPB) cancers, including pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA), are among the deadliest malignancies due to late-stage diagnosis and limited curative options. Conventional tissue biopsies are often invasive and insufficient for longitudinal monitoring. This review synthesizes the current available literature on liquid biopsy, a minimally invasive approach that uses analysis of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) in serum, plasma, or bile, to enable better early detection, surveillance, and treatment monitoring of HPB cancers.

METHODS: A search of PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Google Scholar identified peer-reviewed studies published between April 2016 and July 2025 using the key terms "liquid biopsy", "ctDNA", "cfDNA", "pancreatic", "hepatobiliary", "liver", "cholangiocarcinoma", and "gallbladder", combined with "early detection", "screening", "surveillance", "minimal residual disease", and "monitoring". Preprints, conference abstracts, and editorials were excluded, and no language restrictions were applied. Fifty-eight studies met the inclusion criteria.

KEY CONTENT AND FINDINGS: Recent studies report strong diagnostic performance for early-stage disease, with sensitivities ranging from 63% to 91% and area under the curve (AUC) values often exceeding 0.90 using next-generation sequencing (NGS), methylation profiling, and fragmentomics. Liquid biopsy has also demonstrated improved identification and detection of cancer-specific gene markers. Significant improvements in early detection and prognostication have been shown for PDAC with KRAS, TP53, SMAD4, and cfDNA methylation panels, and for CCA with FGFR2, IDH1/2, and BAP1 mutations detected in bile-derived cfDNA. In HCC, alterations in TERT promoter, TP53, CTNNB1, along with methylation markers such as RASSF1A, APC, and GSTP1, have predicted early disease and recurrence. Longitudinal ctDNA profiling further enables monitoring of minimal residual disease (MRD) and therapeutic resistance.

CONCLUSIONS: Liquid biopsy provides a powerful, minimally invasive tool for early detection, MRD assessment, and real-time disease monitoring in HPB cancers. Despite promising results, broader clinical adoption is limited by assay variability and the need for standardization and prospective validation. Continued innovation and large-scale studies may establish liquid biopsy as a transformative tool for early detection and personalized management of HPB cancers.

PMID:42145022 | DOI:10.21037/cco-2025-aw-135

Expert Rev Mol Diagn. 2026 May 17:1-21. doi: 10.1080/14737159.2026.2673947. Online ahead of print.

ABSTRACT

INTRODUCTION: Liquid biopsy is a noninvasive diagnostic and monitoring method that provides molecular information about disease by analyzing tumor-derived biomaterials obtained from body fluids-primarily blood, as well as plasma, urine, saliva, and others-including circulating tumor DNA (ctDNA), RNA, circulating tumor cells, and exosomes. Consequently, liquid biopsy has become one of the most intensely investigated and rapidly evolving fields in contemporary oncology.

AREAS COVERED: This narrative review covers the molecular components and isolation techniques underlying liquid biopsy platforms, and examines their clinical applications across prostate cancer, bladder cancer, renal cell carcinoma, and testicular germ cell tumors, encompassing pre-biopsy risk stratification, treatment-response monitoring, detection of resistance mechanisms, and minimal residual disease surveillance.

EXPERT OPINION: Clinical utility is now the main barrier to routine adoption of liquid biopsy in genitourinary cancers. Prospective studies must demonstrate that liquid biopsy-guided strategies, including biopsy avoidance, perioperative MRD driven escalation or de-escalation, and adaptation of therapy in the metastatic setting, improve clinically meaningful outcomes and are cost-effective. Standardized pre-analytical procedures, harmonized reporting thresholds, and clear management algorithms for discordant results will be essential for reliable real world implementation.

PMID:42130297 | DOI:10.1080/14737159.2026.2673947

Int J Mol Sci. 2026 Apr 29;27(9):3951. doi: 10.3390/ijms27093951.

ABSTRACT

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with prognosis critically dependent on the stage at diagnosis. Traditional tissue biopsy presents well-known limitations, including tumor heterogeneity and invasiveness. Liquid biopsy, encompassing the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and other cell-free biomarkers, has emerged as a transformative approach for non-invasive tumor profiling. This comprehensive narrative review outlines the recent evidence published on the current state and future perspectives of liquid biopsy in CRC, with a focused emphasis on the role of artificial intelligence (AI), machine learning (ML), and deep learning (DL) in data analysis and clinical translation. Methods: A narrative review of the literature was conducted by searching PubMed/MEDLINE, EMBASE, and ClinicalTrials.gov for articles published between January 2020 and January 2026, using a predefined Boolean search string combining terms related to liquid biopsy biomarkers, colorectal cancer, and artificial intelligence methodologies. Filters were applied to include only English-language human studies. Additional relevant sources were consulted to ensure comprehensive coverage of the available literature. Liquid biopsy platforms, particularly ctDNA sequencing and methylation profiling, demonstrate increasing clinical utility across the CRC care continuum from population screening to post-surgical minimal residual disease (MRD) detection and real-time therapy monitoring. AI-driven analytical frameworks, including Random Forest, Convolutional Neural Networks, LSTM models, and more recently Large Language Models (LLMs), substantially augment the sensitivity and specificity of liquid biopsy interpretation, enabling multimodal data integration. The convergence of liquid biopsy technology and AI-driven analytics represents a paradigm shift toward precision oncology in CRC. Remaining challenges include analytical standardization, model explainability, regulatory harmonization, and equitable access. Future integration of federated learning frameworks and LLM-based clinical decision support tools will be essential for responsible clinical translation.

PMID:42123533 | PMC:PMC13163859 | DOI:10.3390/ijms27093951

Clin Chim Acta. 2026 Mar 31;588:120992. doi: 10.1016/j.cca.2026.120992. Online ahead of print.

ABSTRACT

Bladder cancer diagnosis and surveillance remain anchored in cystoscopy and urine cytology, despite their invasiveness, operator dependence, and limited sensitivity for low-grade or flat lesions. These constraints have accelerated interest in liquid biopsy approaches that provide noninvasive, real-time molecular insights into tumor biology. This narrative review examines emerging evidence on three key classes of circulating biomarkers, namely, circulating tumor DNA (ctDNA), exosomes, and circulating tumor cells (CTCs), and their expanding roles in diagnosis, prognosis, and treatment guidance. ctDNA reflects tumor-specific genomic alterations and shows particular strength in detecting minimal residual disease, identifying early molecular relapse, and monitoring therapeutic response, although its diagnostic sensitivity remains moderate. Urinary exosomes demonstrate some of the highest diagnostic accuracies among liquid biopsy platforms, with multimarker RNA panels achieving sensitivities and specificities above 90%, while their diverse cargo of miRNAs, mRNAs, and lncRNAs provides robust prognostic information linked to recurrence and survival. CTCs, although technically challenging to isolate owing to their phenotypic heterogeneity, offer valuable insights into tumor aggressiveness, metastatic potential, and treatment responsiveness, especially in muscle-invasive disease. Advances in ultrasensitive sequencing, microfluidic CTC capture, and multi-omics integration are accelerating clinical translation. Collectively, circulating biomarkers are poised to complement and, in selected contexts, transform bladder cancer management by enabling earlier detection, individualized risk stratification, and more precise therapeutic decision-making.

PMID:41933678 | DOI:10.1016/j.cca.2026.120992

Eur J Cancer. 2026 Mar 19;239:116676. doi: 10.1016/j.ejca.2026.116676. Online ahead of print.

ABSTRACT

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker in melanoma, with higher sensitivity for tumor burden detection than conventional diagnostics. While well established in research, clinical routine implementation remains pending. Key global questions concern optimal clinical applications and barriers to adoption.

METHODS: A web-based survey of 116 members of the Melanoma World Society Study Group assessed international expert opinions on ctDNA utility across predefined clinical scenarios. The questionnaire included 18 general questions on ctDNA use and 5 clinical vignettes with de-identified patient data and retrospectively obtained ctDNA results.

RESULTS: ctDNA was rated most valuable for detecting minimal residual disease (mean score 3.63), surveillance of recurrent disease (3.85), and stage IV melanoma (3.82), with limited utility in early stages. Experts considered ctDNA superior to S100 and LDH for early relapse detection and identifying progressive disease. Most participants (80%) agreed that ctDNA correlates with radiographic response, and 82% favored its integration into routine follow-ups. In urgent high-tumor-burden settings, 82.8% would initiate BRAFi/MEKi therapy based on ctDNA if tissue analysis was pending, and 93.9% if unavailable. For central nervous system lesions, 62% did not support blood ctDNA, while 66% considered cerebrospinal fluid valuable. Pragmatic approaches with small to mid-size targeted panels and short turnaround times were preferred. Major barriers included the need for prospective trials (85%), standardized guidelines (83%), and reimbursement policies (82%).

CONCLUSION: Key opinion leaders regarded ctDNA as a valuable adjunct selected melanoma scenarios. Validation through prospective studies, guideline development, and reimbursement frameworks are essential for broader clinical implementation.

PMID:41932032 | DOI:10.1016/j.ejca.2026.116676

ESMO Real World Data Digit Oncol. 2026 Jan 14;11:100652. doi: 10.1016/j.esmorw.2025.100652. eCollection 2026 Mar.

ABSTRACT

BACKGROUND: Malignant tumors release circulating tumor DNA (ctDNA) into the bloodstream, providing insights into tumor-specific mutations and pathways driving cancer progression. ctDNA testing is currently approved as a type of liquid biopsy to monitor disease burden and detect minimal residual disease (MRD). This study aimed to evaluate the adoption of ctDNA testing in a community oncology practice and assess the overall diagnostic performance of ctDNA and its association with disease progression in stage IV colorectal cancer (CRC), as determined by imaging studies.

PATIENTS AND METHODS: This retrospective study analyzed the medical records of 88 patients with gastrointestinal cancers (80 CRC, 5 gastric, 3 esophageal) who underwent ctDNA molecular testing between January 2020 and April 2022. Electronic medical records from patients aged ≥21 years who had two or more ctDNA tests with concurrent imaging studies or a pathology-confirmed CRC, gastric cancer, or esophageal cancer diagnosis were evaluated.

RESULTS: At baseline, 47 (53.4%) patients had negative and 41 (46.6%) had positive results. Most patients had CRC (90.1%). In stage IV CRC, ctDNA was increasing before radiologic progression in all documented cases (100%), with a median lead time of 2.5 months (range 0.5-15 months). In early-stage CRC (I-III), ctDNA preceded radiologic progression in 40% of cases, with a median lead time of 6 months (range 6-10 months).

CONCLUSIONS: Using real-world data, we report the first-time results of the ctDNA testing adoption in a community oncology setting among patients with gastrointestinal cancers, predominantly CRC. Our findings suggest that integration of ctDNA testing may support disease monitoring in routine clinical practice.

PMID:41930304 | PMC:PMC13040887 | DOI:10.1016/j.esmorw.2025.100652

Cancer Epidemiol Biomarkers Prev. 2026 Apr 1;35(4):491-493. doi: 10.1158/1055-9965.EPI-25-1971.

ABSTRACT

Recently, stool- and blood-based cancer screening kits have been approved in clinical practice as convenient and noninvasive methods for colon cancer screening. One such test in long-standing practice has included the fecal immunochemical test (FIT), wherein home-based testing has rendered it a convenient initial assay to complement screening colonoscopy, despite limitations in diagnostic performance. In a recent original study published in the journal by Nguyen and colleagues, the feasibility and performance of combining FIT with circulating tumor cell (CTC) enumeration for predicting colorectal neoplasia and the risk of developing colorectal cancer were described. In this commentary, we highlight the potential of this combination as a novel colorectal cancer screening technique. The introduction of CTC as a potential colorectal cancer screening assay is timely, given the emergence of liquid biopsies that hold promise in their ability to detect a multitude of cancer-specific signals, from the detection of minimal residual disease to the detection of molecular alterations for precision therapies in oncology. We place the importance of their results in the context of the evolving landscape of stool- and blood-based colorectal cancer screening tests involving multitarget fecal DNA and cell-free DNA assays. See related article by Nguyen et al., Cancer Epidemiol Biomarkers Prev 2026;35:79-87.

PMID:41918361 | DOI:10.1158/1055-9965.EPI-25-1971

Cancer Biol Med. 2026 Mar 30:j.issn.2095-3941.2026.0045. doi: 10.20892/j.issn.2095-3941.2026.0045. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) remains a major global health burden characterized by late-stage diagnosis and high postoperative recurrence rates. This review presents a surgery-centered precision management framework integrating 3 synergistic components: early detection, precision surgery, and recurrence prevention. Early detection strategies incorporate multiparameter risk models including the gender, age, AFP-L3, AFP, and DCP (GALAD) as well as age, sex, AFP, and PIVKA-II (ASAP) scores, alongside circulating tumor DNA methylation-based liquid biopsy, thus enabling tumor identification at stages amenable to curative resection. Precision surgery optimizes patient selection through refined staging systems including the Chinese liver cancer staging (CNLC), and functional assessments including the albumin-bilirubin (ALBI) grade, whereas conversion therapy and minimally invasive approaches extend surgical eligibility to selected patients with intermediate-stage disease. To mitigate the risk of postoperative recurrence, distinguishing between early and late recurrence patterns and monitoring minimal residual disease are critical strategies. Perioperative systemic therapies, particularly immune checkpoint inhibitor-based combinations, show promise for eradicating micrometastatic disease. This integrated framework provides a cohesive, evidence-based approach to personalized HCC management aimed at maximizing curative potential and long-term survival.

PMID:41913379 | DOI:10.20892/j.issn.2095-3941.2026.0045