Biochim Biophys Acta Rev Cancer. 2026 Sep 15:189717. doi: 10.1016/j.bbcan.2026.189717. Online ahead of print.

ABSTRACT

Breast cancer deaths are mainly caused by metastasis to distant organs, not by the primary tumor. Bone, lung, liver, and brain are the most common metastatic sites, each showing different clinical behaviors and treatment responses-a pattern often called metastatic organotropism. Bulk omics can provide tissue-level information, but they fall short in identifying rare metastasis-initiating clones or capturing how tumor cells adapt to distinct organ microenvironments. With recent progress in single-cell sequencing, multi-omics integration, and spatial profiling, it is now possible to study metastasis at much finer cellular and spatial resolution. In this review, we synthesize current evidence from two complementary perspectives. First, we summarize pan-organ programs associated with metastatic competence, including partial epithelial-mesenchymal transition, lineage plasticity, stem-like states, stress tolerance, metabolic flexibility, immune evasion, and stromal-vascular remodeling. Second, we discuss how these programs are reshaped by organ-specific microenvironments: osteolytic and mixed bone remodeling and marrow dormancy in bone, inflammatory vascular niches in lung, tolerogenic antigen presentation and hepatic metabolism in liver, and blood-brain/blood-tumor barrier constraints, glial crosstalk, neuronal interactions, and lipid-metabolic adaptation in brain. We also highlight how CTC/CTM profiling, spatial mapping, and longitudinal integration refine the understanding of dissemination, dormancy, colonization, outgrowth, and treatment resistance. Although these approaches hold translational promise, most remain at the discovery or early validation stage and require assay simplification, prospective testing, and cross-center standardization. Overall, single-cell and spatial multi-omics are reframing breast cancer metastasis as a dynamic, multi-stage, and tissue-shaped process, providing a foundation for future biomarker development and mechanism-guided therapeutic strategies.

PMID:42744123 | DOI:10.1016/j.bbcan.2026.189717

Biosci Trends. 2026 May 21. doi: 10.5582/bst.2026.01000. Online ahead of print.

ABSTRACT

Oncolytic adenovirus H101 has shown antitumor activity in hepatocellular carcinoma (HCC), but the molecular determinants of treatment response remain unclear. In this study, a Hepa1-6 subcutaneous tumor model was established in C57BL/6 mice and treated with intratumoral H101, followed by integrated transcriptomic and proteomic analyses to identify candidate genes associated with H101 response. PRXL2B was selected for further investigation using public multi-omics datasets, tissue microarray-based immunohistochemistry, in vitro functional assays, mechanistic analyses, and in vivo validation experiments. Integrated multi-omics analyses identified PRXL2B as a candidate gene downregulated after H101 treatment. Public datasets and tissue-based validation further showed that PRXL2B was upregulated in HCC tissues. In MHCC97H and HCCLM3 cells, PRXL2B knockdown inhibited proliferation, migration, and invasion, promoted apoptosis and cell-cycle arrest, and enhanced the antitumor effect of H101. Mechanistically, PRXL2B silencing reduced AKT phosphorylation and PD-L1 expression. In vivo, PRXL2B knockdown suppressed tumor growth, and the combination of PRXL2B knockdown and H101 produced the strongest antitumor effect. These findings indicate that PRXL2B promotes malignant phenotypes in HCC and may modulate H101 efficacy through the PI3K/AKT/PD-L1 axis. Targeting PRXL2B may therefore represent a potential strategy to enhance the therapeutic efficacy of oncolytic virus therapy in HCC.

PMID:42161529 | DOI:10.5582/bst.2026.01000

Cell Rep. 2026 May 26;45(5):117215. doi: 10.1016/j.celrep.2026.117215. Epub 2026 Apr 28.

ABSTRACT

Early-stage lung adenocarcinoma (LUAD) in never smokers exhibits distinct biological features, yet the metabolic programs driving early invasion remain unclear. We integrate proteomic and lipidomic profiling of primary LUAD tumors from never smokers, matched normal adjacent tissues (NATs), and benign pulmonary nodules (BPNs). Integrated multi-omics analysis reveals coordinated dysregulation of lipid metabolism and immune signaling in early LUAD. Proteome-based network fusion stratifies invasive LUAD into immune-metabolic synergistic (IMS) and metabolic-stress-driven (MSD) subtypes. IMS tumors retain apolipoprotein-associated lipid modules and favorable immune features, whereas MSD tumors exhibit stress-response programs. Mechanistically, APOA1 and APOC1 emerge as key nodes linking lipid homeostasis to invasion, and their depletion promotes LUAD cell migration and invasion. We establish a two-protein, four-lipid diagnostic panel demonstrating robust performance across tissue and plasma cohorts. These findings provide a molecular basis for early detection and risk stratification in never smokers.

PMID:42054209 | DOI:10.1016/j.celrep.2026.117215