Nat Med. 2026 Oct 2. doi: 10.1038/s41591-026-04673-3. Online ahead of print.

ABSTRACT

Urine biomarkers promise to improve noninvasive detection and molecular characterization of genitourinary malignancies. Here we describe urine random priming and affinity capture of cell-free RNA (cfRNA) fragments for enrichment analysis by sequencing (uRARE-seq), a liquid biopsy method for urine cfRNA profiling, and apply it to 683 urine samples from patients with cancer and controls. Urine cfRNA contained transcripts from genitourinary tissues and, in patients with prostate, kidney or bladder cancer, tumor-derived transcripts. uRARE-seq demonstrated 95% sensitivity at 90% specificity for detecting localized bladder cancer. The method outperformed urine tumor DNA analysis and was unaffected by the presence of field-effect mutations. Urine cfRNA analysis also sensitively detected minimal residual disease and distinguished complete molecular responses after surgery from those after intravesical Bacillus Calmette-Guérin (BCG). Pretreatment urine from complete responders to BCG was enriched for T cell and other immune signatures, suggesting a preexisting antitumor immune response, whereas nonresponders showed higher expression of proliferation-related genes. In pretreatment urine from 114 patients, this biological difference enabled development of a biomarker predicting likelihood of response to BCG versus chemotherapy (area under the curve 0.93) that was strongly associated with risk of recurrence. Urine cfRNA analysis is therefore a promising biomarker approach for bladder cancer and potentially other urologic malignancies, although prospective studies are needed to assess its clinical utility.

PMID:42827132 | DOI:10.1038/s41591-026-04673-3

Clin Chim Acta. 2026 Oct 2;594:122871. doi: 10.1016/j.cca.2026.122871. Online ahead of print.

ABSTRACT

Head and neck cancers (HNCs) represent one of the most prevalent and lethal types of cancer, accounting for 4.7% of annual cancer new cases and 4.9% of cancer-related mortalities. These high prevalence and mortality rates have positioned HNCs as a global health issue. Despite advances in disease treatment methods, the prognosis of patients with advanced or recurrent diseases remains poor. The difficulty of early-stage diagnosis of HNCs is one of the primary contributors to this reduced long-term survival. Currently available diagnostic and disease-monitoring tools, such as tissue biopsy and imaging techniques, are associated with several limitations, including invasiveness, limited repeatability, and limited sensitivity for detecting minimal residual disease (MRD) and microscopic metastases. In recent years, liquid biopsy has emerged as a promising approach, enabling minimally invasive detection of tumor-related biomarkers in body fluids. This review aims to provide a comprehensive overview of the progress and pitfalls of liquid biopsy in the context of HNCs. In this regard, we discuss the principles of liquid biopsy, applicable biomarker types, sample sources, and advanced detection methods. Furthermore, the current status of liquid biopsy in clinical trials of HNCs and the challenges of its clinical translation are also comprehensively explored.

PMID:42826825 | DOI:10.1016/j.cca.2026.122871

Biomedicines. 2026 Aug 25;14(9):1898. doi: 10.3390/biomedicines14091898.

ABSTRACT

Background/Objectives: Hepatocellular carcinoma (HCC) is the most prevalent primary liver tumor and is often diagnosed at advanced stages with very poor therapeutic response, leading to high mortality. Thus, new therapeutic strategies and biomarkers are urgently needed. We previously showed that the combination of loratadine, raloxifene, and sorafenib exerts synergistic cytotoxicity on HCC cells. Here, we explored potential molecular mechanisms underlying the anticancer effects of this combination using multiomics analyses. Methods: We performed proteomic analyses based on mass spectrometry, transcriptomic analyses using the Clariom D Plus human microarray (Affymetrix), and metabolomic analyses based on nuclear magnetic resonance to investigate the profile changes induced by the drug combination in HuH7 cells. Bioinformatic analyses were applied to associate the omics changes with biological functions, molecular interactions, and clinical relevance in terms of patient survival. Results: We identified several molecules whose expression changed in response to treatment across the three omics profiles analyzed. Some of them were found to be involved in hallmarks of cancer, including sustained proliferation, evasion of growth suppressors, and resistance to cell death. Integrated multi-omics analyses revealed that the drug combination suppresses critical oncogenic drivers (C7orf50, NUP188, and HS2ST1) and that the mitotic cell cycle process, DNA synthesis and cholesterol biosynthesis are the primary pathways affected. Protein-protein interaction analysis revealed five key hubs (KIF2C, PCNA, TRIP13, NDC80, and RPA3), whose expression in HCC is associated with poor clinical prognosis. Conclusions: The combined treatment rewired molecular networks involved in HCC progression. These findings identify clinically relevant molecular targets associated with poor prognosis and provide mechanistic insights into the synergistic anticancer activity of this drug combination.

PMID:42792641 | PMC:PMC13604568 | DOI:10.3390/biomedicines14091898