Diagn Cytopathol. 2025 Nov;53(11):580-591. doi: 10.1002/dc.70009. Epub 2025 Sep 4.

ABSTRACT

Colorectal cancer (CRC) is a major global health burden, ranking among the leading causes of cancer-related deaths. Despite improvements in screening and treatment, challenges such as late-stage diagnosis, high recurrence rates, and therapy resistance continue to impede optimal outcomes. Liquid biopsy, a minimally invasive technique that analyzes tumor-derived components in bodily fluids-including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs)-is emerging as a powerful tool to transform CRC management across the disease continuum. This review provides a comprehensive overview of liquid biopsy's current and emerging applications in CRC. We examine its role in early detection, where sensitive ctDNA-based assays and epigenetic biomarkers have demonstrated the ability to identify CRC at asymptomatic or early stages, potentially improving screening uptake and compliance. Furthermore, we explore how liquid biopsy enables dynamic monitoring of treatment response and clonal evolution, facilitating the timely identification of resistance mutations and supporting personalized therapy adjustments. Innovations in multi-omics integration, artificial intelligence, and ultra-sensitive sequencing technologies are also discussed as pivotal advancements that enhance the clinical utility of liquid biopsy. Despite significant progress, the widespread adoption of liquid biopsy faces several hurdles, including assay standardization, sensitivity for low-shedding tumors, regulatory approval, and cost-effectiveness. Continued research, validation in large prospective trials, and harmonization of testing protocols are essential to overcome these challenges. Ultimately, liquid biopsy holds the potential to become a cornerstone of precision oncology in CRC, enabling earlier intervention, more tailored treatment strategies, and improved patient outcomes.

PMID:40905096 | DOI:10.1002/dc.70009

Cell. 2025 Aug 22:S0092-8674(25)00922-5. doi: 10.1016/j.cell.2025.08.008. Online ahead of print.

ABSTRACT

Performing total RNA profiling on formalin-fixed, paraffin-embedded (FFPE) samples, the predominant sample conservation method in clinical practice, remains challenging for current spatial transcriptomics techniques. Here, we introduce Stereo-seq V2, which employs random primers to capture and sequence RNAs in situ on FFPE sections and provides single-cell resolution. The random-priming-based strategy offers unbiased transcript capturing and uniform gene body coverage, which increase the sensitivity to marker genes, the efficiency of non-polyadenylation (poly(A)) RNA profiling, and immune repertoire coverage. We demonstrated the robust performance of Stereo-seq V2 on clinical FFPE samples using triple-negative breast cancer (TNBC) sections and identified tumor-specific alternative splicing events. In a Mycobacterium tuberculosis (Mtb)-infected mouse model, we monitored gene expression dynamics of host and pathogen transcriptomes simultaneously by utilizing Stereo-seq V2. We also assembled immune repertoires and identified Mtb-specific BCR clones, which could also be observed in human tuberculous lung samples. These results highlight Stereo-seq V2's potential in biomedical research and personalized medicine.

PMID:40882628 | DOI:10.1016/j.cell.2025.08.008