Dig Liver Dis. 2026 Sep 12:S1590-8658(26)00920-5. doi: 10.1016/j.dld.2026.08.021. Online ahead of print.

ABSTRACT

The quality of biological samples is a major determinant of analytical reliability and translational relevance in patients with pancreatic ductal adenocarcinoma (PDAC). However, variability in specimen procurement, handling, transport, processing, and storage can substantially affect tissue integrity and the robustness of downstream analyses. This paper, promoted by the Pathology and Basic Science Task Force of the Italian Association for the Study of the Pancreas (AISP), brings together experts in pathology, molecular biology, translational research, medical oncology, and gastroenterology to provide practical recommendations for the collection, handling, and pre-analytical management of biological samples. Draft recommendations were discussed during dedicated working group meetings and approved by consensus among all authors, supported by key literature. The document identifies the biological specimen as the critical link between patient care, pathology, and research, and provides guidance for clinicians and professionals involved in sample procurement and processing. By addressing the requirements of different analytical platforms, including genomics, organoid generation, immunophenotyping, pharmacogenomics, and multiplex/spatial analyses, this paper aims to reduce pre-analytical variability, improve diagnostic accuracy, and enhance the clinical and translational value of molecular investigations in pancreatic cancer. Standardised procedures across centres may facilitate comparable data collection, support multicentre studies, and strengthen collaboration between clinicians, pathologists, and research laboratories.

PMID:42731958 | DOI:10.1016/j.dld.2026.08.021

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

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

Updates Surg. 2026 Aug 24. doi: 10.1007/s13304-026-02814-4. Online ahead of print.

ABSTRACT

Esophageal cancer (EC) remains a highly lethal malignancy, characterized by late diagnosis, early systemic dissemination, and high recurrence rates. Conventional diagnostic and surveillance strategies have limited sensitivity for early disease detection and minimal residual disease. Liquid biopsy technologies have emerged as promising minimally invasive tools for diagnosis, prognostication, and longitudinal monitoring. This scoping review summarizes current evidence on the clinical utilization of liquid biopsies in esophageal squamous cell and adenocarcinoma. PubMed, EMBASE and Cochrane Library were queried. Inclusion criteria encompassed studies investigating the use of liquid biopsy for EC diagnosis, treatment response evaluation, and prognosis definition. A total of 73 studies reported the role of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), or microRNAs (miRNA). The majority (59%) focused on ctDNA while CTC and miRNA were assessed in 12 and 14 studies, respectively. The reported pooled diagnostic sensitivity and specificity was 71% and 98.6%, respectively, with superior performance in advanced stages (III-IV). Serial ctDNA measurements during neoadjuvant therapy have been reported useful for assessing tumor burden reduction. Additionally, comprehensive ctDNA profiling proved valuable for analysis of tumor heterogeneity and actionable genetic alterations suitable for targeted treatment therapies. Elevated preoperative ctDNA levels correlated with an increased risk of nodal metastasis and postoperative cancer recurrence. ctDNA was also identified as a useful prognostic marker, demonstrating sensitivity and specificity of 49% and 95%, respectively, for survival prediction. Despite limitations related to the various methodologies employed and the lack of laboratory standardization, liquid biopsy constitutes a promising frontier in the surgical management of EC, offering minimally invasive, real-time tool for assessing tumor genetics, genomic heterogeneity, and dynamics of tumor progression. It might enhance early diagnosis, inform neoadjuvant treatment response, and enable postoperative surveillance for residual or recurrent cancer.

PMID:42635711 | DOI:10.1007/s13304-026-02814-4

Immunity. 2026 Apr 8:S1074-7613(26)00075-0. doi: 10.1016/j.immuni.2026.02.005. Online ahead of print.

ABSTRACT

DNA mutations are a well-characterized source of neoepitopes in immunotherapy. Here, we examined the contribution of dysregulated RNA processing to neoantigen production. Leveraging multi-omics and checkpoint inhibitor (CPI) response data from >1,000 patients, we identified reduced activity of the nonsense-mediated mRNA decay (NMD) pathway kinase SMG1 as a predictor of improved CPI response. NMD inhibition through SMG1 targeting stabilized transcripts containing premature termination codons, most of which were of non-mutational origin. This reshaped the major histocompatibility complex class I (MHC class I)-bound immunopeptidome and increased neoantigen abundance to levels comparable to high mutation burden tumors. Functionally, NMD inhibition drove antigen-dependent T cell-mediated tumor cell killing in vitro, promoted activation of tissue-resident T cells in patient-derived models ex vivo, and improved CPI efficacy in vivo. Our findings establish NMD inhibition as a strategy to harness a previously inaccessible source of canonical and non-canonical neoantigens, with the potential to increase tumor immunogenicity across cancers.

PMID:41956098 | DOI:10.1016/j.immuni.2026.02.005