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

Front Immunol. 2026 Mar 16;17:1822612. doi: 10.3389/fimmu.2026.1822612. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2026.1782545.].

PMID:41918731 | PMC:PMC13033988 | DOI:10.3389/fimmu.2026.1822612

Nat Commun. 2026 Mar 23. doi: 10.1038/s41467-026-70798-1. Online ahead of print.

ABSTRACT

Glioblastoma (GBM) remains a lethal brain tumor due to therapy resistance. While autophagy contributes to temozolomide (TMZ) resistance, its regulation is incompletely understood. This study investigates the role of replication factor RFC4, which is associated with poor prognosis and TMZ resistance in GBM. Multi-omics analyses and molecular experiments reveal that TMZ-induced chromatin accessibility enables transcription factor YY1 to bind the RFC4 promoter and upregulate its expression. RFC4, in turn, stabilizes the kinase STK38, which is essential for autophagosome formation. The RFC4-STK38 interaction facilitates BECN1 recruitment, thereby activating autophagy. Phosphorylation of STK38 at T444 stabilizes this complex, whereas a phospho-deficient mutant impairs autophagy. In vivo, RFC4 overexpression confers TMZ resistance, reversible by autophagy inhibition. Thus, our findings identify the RFC4-STK38-BECN1 axis as a mechanism underlying TMZ resistance and a potential target for precision therapy in GBM.

PMID:41872171 | DOI:10.1038/s41467-026-70798-1