CA Cancer J Clin. 2026 Sep-Oct;76(5):e70100. doi: 10.3322/caac.70100.

ABSTRACT

The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence-driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.

PMID:42713910 | PMC:PMC13555834 | DOI:10.3322/caac.70100

CA Cancer J Clin. 2026 Sep-Oct;76(5):e70100. doi: 10.3322/caac.70100.

ABSTRACT

The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence-driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.

PMID:42713910 | DOI:10.3322/caac.70100

Front Immunol. 2026 Aug 20;17:1919864. doi: 10.3389/fimmu.2026.1919864. eCollection 2026.

ABSTRACT

Cholangiocarcinoma is an aggressive biliary tract malignancy in which metastatic relapse and primary or acquired resistance to immunotherapy remain major causes of mortality. Although immune checkpoint inhibitors have improved first-line treatment for advanced biliary tract cancer, most patients do not achieve durable benefit, indicating that immune failure is not explained by a single checkpoint pathway. In this Review, we propose a spatial immune-regulatory continuum for cholangiocarcinoma dissemination. Most direct single-cell and spatial evidence currently derives from intrahepatic cholangiocarcinoma, and its applicability to perihilar and distal disease remains to be established. This continuum begins in the tumor core and invasive front, where malignant cells, cancer-associated fibroblasts, tumor-associated macrophages, endothelial and lymphatic cells, regulatory T cells, immature neutrophils and excluded or dysfunctional cytotoxic T cells form a pro-invasive ecosystem. It then extends through extracellular vesicles, soluble mediators and lymphovascular routes that may educate organotropic pre-metastatic niches. Finally, lymph node, lung, liver, peritoneal and bone microenvironments provide organ-specific extracellular matrix, myeloid and stromal programs that enable immune evasion and metastatic colonization. By integrating clinical evidence, multi-omics studies, single-cell and spatial transcriptomics, extracellular vesicle biology, pre-metastatic niche concepts and emerging therapeutic strategies, we argue that cholangiocarcinoma metastasis should be targeted before overt dissemination whenever possible. In this Review, "metastasis-intercepting immunotherapy" is used as an author-defined conceptual framework for strategies intended to prevent or disrupt the immune-stromal conditions that enable dissemination and colonization, rather than merely shrink established metastatic lesions. Metastasis-intercepting immunotherapy will likely require rational combinations that reprogram the invasive front, restore dendritic-cell-mediated antigen presentation, block tumor-stroma-myeloid circuits, disrupt EV-mediated communication that may contribute to niche formation and select patients using spatial biomarkers rather than bulk immune markers alone.

PMID:42694469 | PMC:PMC13539491 | DOI:10.3389/fimmu.2026.1919864

J Hazard Mater. 2026 Sep 15;516:143449. doi: 10.1016/j.jhazmat.2026.143449. Epub 2026 Aug 30.

ABSTRACT

The global incidence of ulcerative colitis (UC) has significantly increased in rapidly industrializing nations, with numerous studies highlighting environmental exposures, particularly nitrogen dioxide (NO₂), as potential contributors to disease susceptibility. However, the clinical implications and molecular mechanisms linking NO₂ exposure to UC susceptibility remain poorly understood. This study investigated the associations between NO₂ and UC by integrating multi-omics data. We identified a CD8⁺ T cell subpopulation with a distinct phenotype characterized by perforin production, which potentially exacerbated colonic inflammation related to NO₂ exposure. To validate this hypothesis, we established mouse models exposed to NO₂, confirming increased CD8⁺ T cell infiltration and elevated perforin secretion through immunofluorescent (IF) staining. Employing artificial intelligence techniques, we identified Cell Division Cycle 25B (CDC25B) as a gene of interest correlated with putative NO₂-related UC signatures. Finally, through molecular docking (MD) and molecular dynamics simulations (MDS), we identified ozanimod as one of several computationally nominated compounds associated with the CDC25B‑related network; however, none of these computational predictions were experimentally validated in the present study. Collectively, these findings suggest a correlative link between perforin or CD8⁺ T cell-associated colonic inflammation and NO₂-associated UC susceptibility, and nominate CDC25B as a candidate gene for further investigation.

PMID:42679583 | DOI:10.1016/j.jhazmat.2026.143449

Clin Exp Med. 2026 May 10. doi: 10.1007/s10238-026-02160-0. Online ahead of print.

ABSTRACT

The prognostic values of cuproptosis-related genes (CRGs) in gastric cancer with lymph node metastasis (GCLM), especially in the tumor immune microenvironment (TIME), remain unclear. We analyzed the expression, mutation, immunity, drug sensitivity, and prognostic value of CRGs in GCLM using TCGA and GEO cohorts. Consensus clustering was performed to identify CRG subtypes, with differences characterized by multi-omics analysis. A CRG-based prognostic risk score and immune score were constructed for individualized assessment, and the role of CRGs was validated through in vitro and in vivo experiments. Consensus clustering revealed that CRGs were significantly enriched in biological processes related to mitosis and energy metabolism, as well as in immune-related and cancer-associated pathways. Four distinct CRG subtypes were identified, showing marked differences in expression profiles, prognosis, genetic alterations, TIME, and chemotherapeutic drug sensitivity. We developed an exploratory CRG-based prognostic risk score for preliminary individualized assessment, and the functional relevance of CRGs in GCLM was further validated through in vitro experiments. Among these, FDX1, LIAS, DLAT, MTF1, and GLS were identified as key determinants of overall survival in patients with GCLM, with FDX1 emerging as a potential independent prognostic factor. Notably, upregulation of FDX1 significantly suppressed lymph node metastasis of gastric cancer cells in a mouse popliteal lymph node metastasis model. Our data uncovers FDX1 might be a potential favorable prognostic factors in GCLM patients. These findings may improve our understanding of CRGs in GCLM and provide new in-sights for assessing prognosis and developing more effective treatment strategies.

PMID:42107026 | DOI:10.1007/s10238-026-02160-0

Cell Oncol (Dordr). 2026 Mar 23;49(2):60. doi: 10.1007/s13402-026-01194-6.

ABSTRACT

Glycolytic reprogramming is closely associated with the occurrence and progression of gastric cancer. Specifically, the energy derived from glucose metabolism and the cellular proteins by its intermediate products influence gastric cancer development. However, as an important branch of glucose metabolism, sialic acid metabolism and its mediated sialylation modifications remain insufficiently studied in gastric cancer, and their specific relationship with malignant tumor progression requires further exploration. This study employed a multi‑omics approach, integrating metabolomics, single‑cell RNA sequencing, and bulk RNA sequencing analyses, to investigate the metabolic landscape of gastric cancer and its associated alterations. The results indicated that sialic acid is a characteristic metabolite in malignant gastric cancer tissues. It modulates biological functions such as immune response, proliferative activity, and metabolic remodeling within gastric cancer tissues by influencing sialylation modifications. Furthermore, we identified the drug WZ35, which can inhibit the malignant proliferation of gastric cancer by targeting both sialic acid metabolism and sialylated protein modifications. We put forward a conjecture that the metabolism and modification of sialic acid promote the malignant development of gastric cancer, and we discovered that the drug WZ35 has an inhibitory effect on the sialic acid metabolism of gastric cancer.

GRAPHICAL ABSTRACT:

PMID:41870836 | PMC:PMC13009457 | DOI:10.1007/s13402-026-01194-6

Cell Oncol (Dordr). 2026 Mar 23;49(2):60. doi: 10.1007/s13402-026-01194-6.

NO ABSTRACT

PMID:41870836 | DOI:10.1007/s13402-026-01194-6