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

Mol Clin Oncol. 2025 Mar 12;22(5):42. doi: 10.3892/mco.2025.2837. eCollection 2025 May.

ABSTRACT

Before the twentieth century, patients with advanced lung cancer had limited treatment options and chemotherapy was the primary form of treatment, with an overall survival often <0.5 years. However, with advances in society and medical technology, the treatment approaches for advanced non-small cell lung cancer (NSCLC) have markedly changed. Traditional chemotherapy has been gradually replaced by targeted therapy and immunotherapy, leading to the emergence of various new therapeutic options that offer patients more personalized and precise care. This raises the question of what the future holds for the treatment of NSCLC. This review provides a comprehensive analysis of the latest breakthroughs in targeted therapies, immunotherapies, and drugs for antibody-drug conjugates (ADCs), highlights advances in multimodal combination therapy strategies, and explores the causes of resistance and the challenges that exist in overcoming it. In particular, this review provides unique insights into key directions for future research in NSCLC, such as personalised treatment strategies and biomarker exploration based on multi-omics data, aiming to provide new inspiration for clinical decision-making and research.

PMID:40160297 | PMC:PMC11948471 | DOI:10.3892/mco.2025.2837