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Who Truly Benefits from Anti-EGFR Rechallenge in Metastatic Colorectal Cancer? From Clinical Enrichment to ctDNA-Guided Molecular Hyperselection.

Later-line treatment of metastatic colorectal cancer (mCRC) remains challenging because established salvage options often provide limited ob … nce of detectable RAS/BRAF and, where feasible, EGFR extracellular-domain resistance alterations in circulating tumor DNA (ctDNA). Broader molecular hyperselection and longitudinal ctDNA-guided decision models are promising but remain less standardized and require prospective validation. Outcomes across studies differ not only because of selection depth, but also becau …

Utility of Urinary Extracellular Vesicles for Colorectal Cancer: Comparison of DNA Quality and MRD Detection.

This study evaluated the feasibility of urinary extracellular vesicles (EVs) as a liquid biopsy source for colorectal cancer (CRC) using two predefined cohorts: 97 patients for analytical validation and 63 patients for postoperative survival analysis. We compared urinary EVs, urinary cell-free tumor DNA (ctDNA), plasma EVs, and plasma ctDNA across multiple molecular dimensions, and assessed the utility of urinary EV-DNA for minimal residual disease (MRD) detection. Urinary EVs exhibited larger particle size (median 175.6 nm) and markedly higher purity, demonstrated by a substantially broader p

Functional footprints of homologous recombination deficiency in prostate cancer revealed by ctDNA fragmentation and transcription factor accessibility.

BACKGROUND: Homologous recombination deficiency (HRD) is a predictive biomarker for response to PARP inhibitors and platinum-based therapies in prostate cancer (PCa). However, current diagnostic approaches, often limited to BRCA1/2 mutation testing or genomic scars, fail to capture the full spectrum of HRD. Tissue-based testing is further hampered by tumour heterogeneity and biopsy limitations in patients with metastatic bone disease. This study aimed to develop a noninvasive, multimodal ctDNA-based strategy for comprehensive HRD profiling in advanced PCa. METHODS: We analysed plasma-derived

Genomics in Lung Cancer: A Scoping Review of the Role of ctDNA in Non-Advanced Non-Small-Cell Lung Cancer in the Prediction of Prognosis After Multimodality Therapeutic Approaches.

Background: Circulating tumor DNA (ctDNA), shed into bodily fluids by cancer cells through apoptosis, necrosis, or active secretion, is currently used in the field of genomic investigation in clinical settings, primarily for advanced stages of non-small-cell lung cancer (NSCLC). However, its potential role in guiding the multi-omic approach to early-stage NSCLC is emerging as a promising area of investigation. Efforts are being made to integrate the genomics not only in surgery, but also in the definition of long-term prognosis after surgical or radiotherapy and for the prediction of recurrenc…

Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats.

BACKGROUND: Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic nondiseased cells, DNA released from dead cancer cells varies in size. We developed a novel method to measure the ratio of longer to shorter DNA fragments (DNA integrity) in serum as a potential biomarker for patients with colorectal cancer (CRC) or periampullary cancers (PACs). METHODS: Sera from 32 patients with CRC (3 stage I, 14 stage II, 6 stage III, and 9 stage IV patients), 19 patients with PACs (2 stage I, 9 stage II, 1 stage III, and 7 s

Early detection of multiple cancers: the era of methylation-based liquid biopsy.

Liquid biopsy based on circulating cell-free DNA (cfDNA) methylation has become a leading non-invasive strategy for multi-cancer early detection (MCED). Aberrant DNA methylation arises at the early stage of tumorigenesis and displays cancer-type-specific signatures, enabling early capture of tumor-derived epigenetic signals. High-throughput sequencing, digital PCR and machine learning algorithms have greatly improved the sensitivity and specificity of methylation-based assays. Large-scale clinical trials including CCGA, PATHFINDER, THUNDER and GUIDE have validated that MCED tests achieve high

Limitations in the Use of Serum Epidermal Growth Factor Receptor Mutations as Prognostic Markers for Non-Small-Cell Lung Cancer.

OBJECTIVES: In this study, we surveyed patients with advanced non-small-cell lung cancer (NSCLC) who were undergoing tyrosine kinase inhibitor (TKI)-targeted therapy. Our aim was to determine whether epidermal growth factor receptor (EGFR) mutations in serum circulating tumor (ct)DNA are useful prognostic markers for NSCLC. Sujects and Methods: Serum samples were collected from 300 patients with NSCLC that included adenocarcinoma (ADC, n = 155) and squamous cell carcinoma (SCC, n = 145). DNA was extracted from the sera for the nested polymerase chain reaction (PCR) amplification of EGFR exons

Genitourinary Oncology Highlights from the European Society for Medical Oncology Annual Meeting 2025: Advances in Renal Cell Carcinoma and Muscle-Invasive Bladder Cancer.

<p>Background: At ESMO 2025, practice-changing advances in genitourinary oncology emerged for renal cell carcinoma (RCC) and muscle-invasive … IC RCC transcriptomic stratification and circulating markers like kidney-injury molecule type 1 and circulating tumor DNA strongly support a broader transition toward tailored therapy. Key Messages: Perioperative enfortumab vedotin plus pembrolizumab offers a major survival benefit for cisplatin-ineligible bladder cancer patients. Overall, early-stage RCC benefits sign …

Predicting cancer origins with a DNA methylation-based deep neural network model.

Cancer origin determination combined with site-specific treatment of metastatic cancer patients is critical to improve patient outcomes. Existing pathology and gene expression-based techniques often have limited performance. In this study, we developed a deep neural network (DNN)-based classifier for cancer origin prediction using DNA methylation data of 7,339 patients of 18 different cancer origins from The Cancer Genome Atlas (TCGA). This DNN model was evaluated using four strategies: (1) when evaluated by 10-fold cross-validation, it achieved an overall specificity of 99.72% (95% CI 99.69%-

Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.

Small cell lung cancer is one of the most aggressive malignancies, characterized by rapid tumor growth, early metastatic spread and extremel … lly, we consider the growing potential of liquid biopsy strategies, which exploit the high level of circulating tumor DNA in patients with this disease to detect clinically relevant genomic alterations and monitor tumor evolution. Overall, this review highlights both the opportunities and challenges associated with molecular stratification in small cell lung cancer. Th …

Prolonged response to treatment based on cell-free DNA analysis and molecular profiling in three patients with metastatic cancer: a case series.

BACKGROUND: Patients with advanced and/or metastatic solid tumors have limited treatment options. Mutations that serve as biomarkers of carcinogenesis can be found in cell-free DNA of patients' plasma. Analysis of circulating tumor DNA (ctDNA) was developed as a non-invasive, cost-effective alternative to tumor biopsy when such biopsy is not technically feasible or it is associated with high risk for complications. The role of ctDNA in precision oncology is promising but its clinical significance across tumor types remains to be validated. We report a case series of three heavily pretreated pa…

Quantifying Protein Temporal Changes with Mass Spectrometry in Plasma Samples from Breast Cancer Patients Undergoing Radiotherapy.

Radiation therapy (RT) is a central component of cancer treatment, including breast cancer, and primarily damages DNA in cancer cells, causing cell death. However, secondary effects of RT that may influence tumor and normal tissue both within and beyond the site of irradiation are not well characterized, particularly at the level of the circulating blood proteome. In this study, isotopic acrylamide labeling of proteins and high-resolution LC-MS/MS were used to analyze plasma proteins from breast cancer patients before, during, and after RT. Clustering analysis was used to group proteins accord

Rare, Yet Targetable: New Perspectives on Ampullary Carcinomas.

Ampullary carcinoma (AC) is a rare gastrointestinal malignancy with dual intestinal and pancreatobiliary differentiation, complicating diagn … igh-impact targets, followed by comprehensive profiling at first progression. Liquid biopsy, plasma circulating tumor DNA (ctDNA), or bile-derived DNA may complement tissue and help identify the dominant lineage. Research priorities include ampulla-enriched umbrella trials, explicit AC subcohorts in tissue-agnostic studies, and ctDNA-informed endpoints. This lineage-fi …

Parp7 generates an ADP-ribosyl degron that controls negative feedback of androgen signaling.

The androgen receptor (AR) transduces the effects of circulating and tumor-derived androgens to the nucleus through ligand-induced changes in protein conformation, localization, and chromatin engagement. Defining how these events are integrated with signal transduction is critical to understand how AR drives prostate cancer and unveil pathway features that are potentially amenable to therapeutic intervention. We describe a novel post-transcriptional mechanism that controls AR levels on chromatin and gene output based on highly selective, inducible degradation. We find that the mono-ADP-ribosyl

Novel Blood-Based Tests for Colorectal Cancer Screening.

Blood-based tests are a novel colorectal cancer (CRC) screening modality that can potentially improve screening uptake due to greater convenience and patient preference for blood tests. To date, 3 blood-based CRC screening tests have completed large validation studies (Epi proColon, Shield, and the Freenome test). Multi-cancer early detection tests are also actively being investigated for their role in CRC screening. Despite various benefits, blood-based screening tests also have several limitations, including low sensitivity for advanced precancerous lesions, low rates of follow-up colonoscop

Integrating Radiogenomics and CSF-Based Liquid Biopsy Sequencing for Precision Neuro-Oncology.

Glioblastoma and diffuse gliomas pose major therapeutic challenges due to marked intratumoral heterogeneity, limited tissue accessibility, and the blood-brain barrier. Tissue-based next-generation sequencing (NGS) remains essential for WHO CNS5 molecular classification, yet it is invasive and poorly suited to serial monitoring. Two complementary non- or minimally invasive approaches have advanced rapidly: radiogenomics, which correlates multiparametric MRI features with genomic alterations, and cerebrospinal fluid (CSF) liquid biopsy sequencing, which detects circulating tumor DNA with high ti…

Patient-specific targeted analysis of circulating tumour DNA in plasma is feasible and may be a potential biomarker in UTUC.

PURPOSE: The prognosis of upper urinary tract urothelial carcinoma (UTUC) is associated with tumour grade (G) and stage. Despite preoperative risk stratification and radical treatment, recurrence and progression are common. Thus, prognostic and monitoring biomarkers are needed. This feasibility study aimed to investigate if targeted analyses on circulating tumour DNA (ctDNA) in plasma could identify tumour-specific gene variants, and thus have potential for further evaluation as a biomarker in UTUC. METHODS: Nine UTUC patients with genetically characterised tumours were included in this prosp

Increase in serum choline levels predicts for improved progression-free survival (PFS) in patients with advanced cancers receiving pembrolizumab.

BACKGROUND: Recent studies have demonstrated that T cells can induce vasodilation in a choline-acetyltransferase dependent manner, leading t … munological Response Evaluation phase II trial (NCT02644369). Samples were analyzed for choline and circulating tumor DNA (ctDNA). Multivariable Cox models were used to assess the association between choline and overall survival (OS) and progression-free survival (PFS) when including ΔctDNAC3 (the change in ctDNA from baseline to cycle 3), cohort, PD-L1 expression and …

Current and Emerging Applications of Droplet Digital PCR in Oncology: An Updated Review.

In the era of personalized medicine and targeted therapies for the management of patients with cancer, ultrasensitive detection methods for tumor genotyping, such as next-generation sequencing or droplet digital polymerase chain reaction (ddPCR), play a significant role. In the search for less invasive strategies for diagnosis, prognosis and disease monitoring, the number of publications regarding liquid biopsy approaches using ddPCR has increased substantially in recent years. There is a long list of malignancies in which ddPCR provides a reliable and accurate tool for detection of nucleic ac

Overview on Molecular Biomarkers for Laryngeal Cancer: Looking for New Answers to an Old Problem.

Laryngeal squamous cell cancer (LSCC) accounts for almost 25-30% of all head and neck squamous cell cancers and is clustered according to the affected districts, as this determines distinct tendency to recur and metastasize. A major role for numerous genetic alterations in driving the onset and progression of this neoplasm is emerging. However, major efforts are still required for the identification of molecular markers useful for both early diagnosis and prognostic definition of LSCC that is still characterized by significant morbidity and mortality. Non-coding RNAs appear the most promising

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… Circulating Tumor DNA and Circulating Tumor Cells: Prospective Search to Improve the Clinical Management of LSCC Patients Cell-free DNA fragments originated from tumor cells—circulating tumor DNA (ctDNA)—can be detected in body fluids such as blood, saliva, urine, and cerebrospinal fluid. …