Cancer Cell Int. 2025 Apr 24;25(1):161. doi: 10.1186/s12935-025-03792-0.

ABSTRACT

BACKGROUND: For patients with nodules detected in imaging that are indeterminate for malignancy, achieving accurate, early, and non-invasive diagnosis of Lung Squamous Cell Carcinoma (LUSC) remains a significant challenge. Therefore, we aimed to establish diagnostic and prognostic models by identifying plasma extracellular vesicles (EVs) associated protein biomarkers specific to LUSC.

METHODS: This study employed a novel nanomaterial, NaY, for the enrichment of EVs from plasma. Validation was conducted through transmission electron microscopy, nanoparticle tracking analyses, and Western blotting. Machine learning algorithms were utilized to compute protein biomarkers associated with LUSC and establish a diagnostic model. Additionally, a prognostic prediction model for LUSC was developed using a combination of 101 machine learning algorithms. Risk scoring of patients was performed to explore the underlying reasons for prognostic differences between high and low-risk groups.

RESULTS: The results of three experiments demonstrate that the new nanomaterial NaY effectively enriches EVs from plasma. Analysis of the enriched profile reveals pathways related to glycolysis/gluconeogenesis and carbon metabolism enriched in plasma EVs of LUSC patients. Thirty-eight LSCC-related EV biomarkers were identified, from which five proteins (TUBB3, RPS7, RPLP1, KRT2, and VTN) were selected to establish a diagnostic model distinguishing between benign and LUSC nodules. The diagnostic efficacy of RPS7 and VTN was further validated in independent samples using ELISA experiments. Furthermore, DPYD, GALK1, CDC23, UBE2L3, RHEB, and PSME1 were determined as potential prognostic biomarkers. Subsequently, risk scores were computed for each sample, classifying all patients into high and low-risk groups. Enrichment analysis revealed that EVs from the high-risk group contained proteins promoting cell proliferation and invasion, while those from the low-risk group were enriched in immune-related protein biomarkers.

CONCLUSIONS: The novel nanomaterial NaY effectively enriches EVs from plasma. Utilizing plasma EV biomarkers, the diagnostic model demonstrates strong discriminative ability between benign and malignant pulmonary nodules in patients.

PMID:40275246 | PMC:PMC12023671 | DOI:10.1186/s12935-025-03792-0

Per Med. 2025 Apr 21:1-10. doi: 10.1080/17410541.2025.2494982. Online ahead of print.

ABSTRACT

Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, with most cases diagnosed at advanced stages, resulting in poor survival rates. Early detection significantly improves outcomes, yet current screening methods, such as low-dose computed tomography (LDCT), are limited by high false-positive rates, radiation exposure, and restricted eligibility criteria. This review highlights the transformative potential of genomic and molecular technologies in advancing the early detection of LC. Key innovations include liquid biopsy tools, such as circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) analysis, which offer minimally invasive approaches to detect tumor-specific genetic and epigenetic alterations. Emerging biomarkers, including methylation signatures, cfDNA fragmentomics, and multi-omics profiles, demonstrate improved sensitivity and specificity in identifying early-stage tumors. Advanced platforms like next-generation sequencing (NGS) and machine-learning algorithms further enhance diagnostic accuracy. Integrated approaches that combine genomic data with LDCT imaging and artificial intelligence (AI) show promise in addressing current limitations by improving risk stratification and nodule characterization. The review also explores multi-cancer early detection assays and precision diagnostic strategies tailored for diverse at-risk populations. By leveraging these advancements, clinicians can achieve earlier diagnoses, reduce unnecessary procedures, and ultimately decrease LC mortality.

PMID:40255184 | DOI:10.1080/17410541.2025.2494982

Nat Rev Urol. 2025 Apr 15. doi: 10.1038/s41585-025-01023-9. Online ahead of print.

ABSTRACT

Liquid biopsies, indicating the sampling of body fluids rather than solid-tissue biopsies, have the potential to revolutionize cancer care through personalized, noninvasive disease detection and monitoring. Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) are promising blood-based biomarkers in bladder cancer. Results from several studies have shown the clinical potential of ctDNA and CTCs in bladder cancer for prognostication, treatment-response monitoring, and early detection of minimal residual disease and disease recurrence. Following successful clinical trial evaluation, assessment of ctDNA and CTCs holds the potential to transform the therapeutic pathway for patients with bladder cancer - potentially in combination with the analysis of urinary tumour DNA - through tailored treatment guidance and optimized disease surveillance.

PMID:40234713 | DOI:10.1038/s41585-025-01023-9

Cytopathology. 2025 Apr 11. doi: 10.1111/cyt.13485. Online ahead of print.

ABSTRACT

The advent of personalised and precision medicine has radically modified the management and the clinical outcome of cancer patients. However, the expanding number of predictive, prognostic, and diagnostic biomarkers has raised the need for simple, noninvasive, quicker, but equally efficient tests for molecular profiling. In this complex scenario, the adoption of liquid biopsy, particularly circulating tumour DNA (ctDNA), has been a real godsend for many cancer patients who would otherwise have been denied the benefits of targeted treatments. Undeniably, ctDNA analysis has several advantages over conventional tissue-based analysis. One advantage is that it can guide treatment decision making, especially when tissue samples are scarce or totally unavailable. Indeed, a simple blood test can inform clinicians on patients' response or resistance to targeted therapies, help them monitor minimal residual disease (MRD) after surgical resections, and facilitate them with early cancer detection and interception. Finally, an equally important advantage is that ctDNA analysis can help decipher temporal and spatial tumour heterogeneity, a mechanism highly responsible for therapeutic resistance. In this review, we gathered and analysed current evidence on the clinical usefulness of ctDNA analysis in solid tumours.

PMID:40219616 | DOI:10.1111/cyt.13485

Sci Data. 2025 Apr 1;12(1):545. doi: 10.1038/s41597-025-04912-1.

ABSTRACT

Diagnosing lung cancer at a curable stage offers the opportunity for a favorable prognosis. The emerging epigenomics analysis on plasma cell-free DNA (cfDNA), including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications, has acted as a promising approach facilitating the identification of lung cancer. And, integrating 5mC biomarker with chest computed tomography (CT) image features could optimize the diagnosis of lung cancer, exceeding the performance of models built on single feature. However, the clinical applicability of integrated markers might be limited by the potential risk of overfitting due to small sample size. Hence, we prospectively collected peripheral blood sample and the paired chest CT images of 2032 patients with indeterminate pulmonary nodules across 5 centers, and constructed a large-scale, multi-institutional, multiomics database that encompass CT imaging data and plasma cfDNA fragmentomic in 5mC-, 5hmC-enriched regions. To our best knowledge, this dataset is the first radio-epigenomic dataset with the largest sample size, and provides multi-dimensional insights for early diagnosis of lung cancer, facilitating the individuated management for lung cancer.

PMID:40169596 | PMC:PMC11961589 | DOI:10.1038/s41597-025-04912-1

Front Oncol. 2025 Mar 13;15:1520717. doi: 10.3389/fonc.2025.1520717. eCollection 2025.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality, primarily due to late stage at diagnosis. This review examines the multifaceted applications of liquid biopsy and circulating tumor DNA (ctDNA) analysis in the diagnosis and management of PDAC. We review the current literature on the technological advancements in liquid biopsy analysis such as next generation sequencing (NGS) and digital droplet PCR (ddPCR) as well as multi-omics technologies, highlighting their potential for accurate molecular subtyping through ctDNA analysis. This review highlights the significant role of ctDNA in the assessment of tumor behavior, disease subtyping, prediction and monitoring of treatment response, and evaluation of minimal residual disease. We discuss the implications of integrating liquid biopsy techniques into clinical practice as well as its challenges and limitations. By drawing insights from recent studies, this review aims to provide a comprehensive overview of how liquid biopsy and ctDNA analysis can enhance early disease management strategies in PDAC. We underscore the need for additional prospective studies and clinical trials to validate its feasibility and accuracy in order to establish clinical utility, with the ultimate goal of routine incorporation into practice to improve patient outcomes and transform the treatment landscape for PDAC.

PMID:40182037 | PMC:PMC11966063 | DOI:10.3389/fonc.2025.1520717

Front Oncol. 2025 Mar 13;15:1520717. doi: 10.3389/fonc.2025.1520717. eCollection 2025.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality, primarily due to late stage at diagnosis. This review examines the multifaceted applications of liquid biopsy and circulating tumor DNA (ctDNA) analysis in the diagnosis and management of PDAC. We review the current literature on the technological advancements in liquid biopsy analysis such as next generation sequencing (NGS) and digital droplet PCR (ddPCR) as well as multi-omics technologies, highlighting their potential for accurate molecular subtyping through ctDNA analysis. This review highlights the significant role of ctDNA in the assessment of tumor behavior, disease subtyping, prediction and monitoring of treatment response, and evaluation of minimal residual disease. We discuss the implications of integrating liquid biopsy techniques into clinical practice as well as its challenges and limitations. By drawing insights from recent studies, this review aims to provide a comprehensive overview of how liquid biopsy and ctDNA analysis can enhance early disease management strategies in PDAC. We underscore the need for additional prospective studies and clinical trials to validate its feasibility and accuracy in order to establish clinical utility, with the ultimate goal of routine incorporation into practice to improve patient outcomes and transform the treatment landscape for PDAC.

PMID:40182037 | PMC:PMC11966063 | DOI:10.3389/fonc.2025.1520717

Cancers (Basel). 2025 Mar 8;17(6):927. doi: 10.3390/cancers17060927.

ABSTRACT

INTRODUCTION: Liquid biopsies provide a less-invasive option to tissue biopsies for the early diagnosis, prognosis, and tailored therapy of colorectal cancer (CRC). CRC is a major cause of cancer-related death, and early identification is essential for improving patient outcomes.

REVIEW: Conventional diagnostic techniques, including colonoscopy and tissue biopsy, may be enhanced by liquid biopsies that examine circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and other indicators present in body fluids. These markers provide significant insights into tumor biology, heterogeneity, and therapeutic response. CTCs detected in early-stage CRC have prognostic significance for disease recurrence and survival, while ctDNA investigation may uncover genetic mutations, epigenetic alterations, and tumor development. The identification of ctDNA in minimal residual disease (MRD) postsurgery correlates with an elevated risk of recurrence and unfavorable prognosis, underscoring its use in assessing treatment effectiveness. Furthermore, non-coding RNAs (ncRNAs) contained inside EVs provide potential prospective biomarkers and therapeutic targets, facilitating diagnosis and treatment assessment. Notwithstanding the potential of liquid biopsies, obstacles persist in assay standardization, sensitivity enhancement, and the management of tumor heterogeneity. Additional extensive research is required to determine their function in clinical practice.

CONCLUSION: Overall, liquid biopsies serve as a potential instrument for real-time monitoring, evaluating therapy responses, and directing individualized therapeutic strategies in CRC patients.

PMID:40149264 | PMC:PMC11940745 | DOI:10.3390/cancers17060927

Mol Biomed. 2025 Mar 20;6(1):18. doi: 10.1186/s43556-025-00257-8.

ABSTRACT

Cancer ranks among the most lethal diseases worldwide. Tissue biopsy is currently the primary method for the diagnosis and biological analysis of various solid tumors. However, this method has some disadvantages related to insufficient tissue specimen collection and intratumoral heterogeneity. Liquid biopsy is a noninvasive approach for identifying cancer-related biomarkers in peripheral blood, which allows for repetitive sampling across multiple time points. In the field of liquid biopsy, representative biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Many studies have evaluated the prognostic and predictive roles of CTCs and ctDNA in various solid tumors. Although these studies have limitations, the results of most studies appear to consistently demonstrate the correlations of high CTC counts and ctDNA mutations with lower survival rates in cancer patients. Similarly, a reduction in CTC counts throughout therapy may be a potential prognostic indicator related to treatment response in advanced cancer patients. Moreover, the biochemical characteristics of CTCs and ctDNA can provide information about tumor biology as well as resistance mechanisms against targeted therapy. This review discusses the current clinical applications of liquid biopsy in cancer patients, emphasizing its possible utility in outcome prediction and treatment decision-making.

PMID:40108089 | PMC:PMC11923355 | DOI:10.1186/s43556-025-00257-8

Oncotarget. 2025 Mar 12;16:140-162. doi: 10.18632/oncotarget.28703.

ABSTRACT

The human genome project ushered in a genomic medicine era that was largely unimaginable three decades ago. Discoveries of druggable cancer drivers enabled biomarker-driven gene- and immune-targeted therapy and transformed cancer treatment. Minimizing treatment not expected to benefit, and toxicity-including financial and time-are important goals of modern oncology. The Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine founded by Drs. John Mendelsohn and Thomas Tursz provided a vision for innovation, collaboration and global impact in precision oncology. Through pursuit of transcriptomic signatures, artificial intelligence (AI) algorithms, global precision cancer medicine clinical trials and input from an international Molecular Tumor Board (MTB), WIN has led the way in demonstrating patient benefit from precision-therapeutics through N-of-1 molecularly-driven studies. WIN Next-Generation Precision Oncology (WINGPO) trials are being developed in the neoadjuvant, adjuvant or metastatic settings, incorporate real-world data, digital pathology, and advanced algorithms to guide MTB prioritization of therapy combinations for a diverse global population. WIN has pursued combinations that target multiple drivers/hallmarks of cancer in individual patients. WIN continues to be impactful through collaboration with industry, government, sponsors, funders, academic and community centers, patient advocates, and other stakeholders to tackle challenges including drug access, costs, regulatory barriers, and patient support. WIN's collaborative next generation of precision oncology trials will guide treatment selection for patients with advanced cancers through MTB and AI algorithms based on serial liquid and tissue biopsies and exploratory omics including transcriptomics, proteomics, metabolomics and functional precision medicine. Our vision is to accelerate the future of precision oncology care.

PMID:40073368 | PMC:PMC11907938 | DOI:10.18632/oncotarget.28703

Klin Onkol. 2025;38(1):32-37. doi: 10.48095/ccko202532.

ABSTRACT

BACKGROUND: Space still exists in the management of patients with colorectal cancer (CRC) for improving risk stratification and thus the precision of treatment tailoring. Quite promising in this regard are biomarkers acquired via liquid biopsy, which is a non-invasive method of body fluid draw, most commonly peripheral blood. A variety of biomarkers associated with the tumor are analyzed, which can have either prognostic or predictive value. Circulating tumor DNA (ctDNA) is one of the most explored tumor biomarkers. Initially, its utility spectrum was only in advanced or metastatic cancers and consisted of molecular profiling and detecting acquired resistance to treatment. Nowadays, the use of circulating tumor DNA has shifted to earlier cancer stages, where it can identify minimal residual disease or diagnose colorectal cancer early. Existing studies show promising potential of these biomarkers, but more information needs to be gathered and information from ongoing studies needs to be obtained in order to use them in everyday practice.

AIM: In this review article, we will discuss ctDNA, its aspects, diag- nostic possibilities and current use in CRC.

PMID:40088434 | DOI:10.48095/ccko202532

J Clin Endocrinol Metab. 2025 Mar 8:dgaf159. doi: 10.1210/clinem/dgaf159. Online ahead of print.

ABSTRACT

The prevalence of diabetes, particularly type 2 diabetes, has reached epidemic proportions globally. The number of patients with type 1 diabetes (T1D) is also increasing rapidly. Despite advancements in understanding the pathogenesis of diabetes, the lack of circulating pancreatic biomarkers and reliable clinical-grade assays remains a major gap in diabetes research, often hindering the ability to adequately assess disease progression and therapeutic responses. This mini-review discusses emerging pancreatic biomarkers with an emphasis on T1D, the limitations of current immunoassays, and the expanding role of mass spectrometry-based assays. Highlights include the recent work within the NIDDK-funded "Targeted Mass Spectrometry Assays for Diabetes and Obesity Research (TaMADOR)" consortium, which aims to develop robust, quantitative, and transferable assays for translational research. The review also emphasizes the importance of proteoform-specific assays for monitoring pancreatic function, including prohormone processing during disease progression or in responses to therapy.

PMID:40056450 | DOI:10.1210/clinem/dgaf159