Senescence-driven molecular subtyping in pancreatic cancer: a multi-omics framework for precision medicine
BMC Cancer. 2025 Dec 15. doi: 10.1186/s12885-025-15341-z. Online ahead of print.
NO ABSTRACT
PMID:41398222 | DOI:10.1186/s12885-025-15341-z
BMC Cancer. 2025 Dec 15. doi: 10.1186/s12885-025-15341-z. Online ahead of print.
NO ABSTRACT
PMID:41398222 | DOI:10.1186/s12885-025-15341-z
Nature Medicine, Published online: 27 October 2025; doi:10.1038/s41591-025-04006-w
The biological clock model LifeClock predicts biological age across all life stages from routine clinical data, revealing distinct pediatric and adult disease risk patterns.Cell Death Discovery, Published online: 16 October 2025; doi:10.1038/s41420-025-02745-w
Evidence of fructose metabolism in colorectal cancerNature Medicine, Published online: 28 August 2025; doi:10.1038/s41591-025-03900-7
Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.Nat Commun. 2025 Aug 22;16(1):7827. doi: 10.1038/s41467-025-63146-2.
ABSTRACT
While dysregulation of polyamine metabolism is frequently observed in cancer, it is unknown how polyamines alter the tumor microenvironment (TME) and contribute to therapeutic resistance. Analysis of polyamines in the plasma of pancreatic cancer patients reveals that spermine levels are significantly elevated and correlate with poor prognosis. Using a multi-omics approach, we identify Serpinb9 as a vulnerability in spermine metabolism in pancreatic cancer. Serpinb9, a serine protease inhibitor, directly interacts with spermine synthase (SMS), impeding its lysosome-mediated degradation and thereby augmenting spermine production and secretion. Mechanistically, the accumulation of spermine in the TME alters the metabolic landscape of immune cells, promoting CD8+ T cell dysfunction and pro-tumor polarization of macrophages, thus creating an immunosuppressive microenvironment. Small peptides that disrupt the Serpinb9-SMS interaction significantly enhance the efficacy of immune checkpoint blockade therapy. Together, our findings suggest that targeting spermine metabolism is a promising strategy to improve pancreatic cancer immunotherapy.
PMID:40846845 | PMC:PMC12373741 | DOI:10.1038/s41467-025-63146-2
Oncogenesis, Published online: 08 August 2022; doi:10.1038/s41389-022-00421-7
Methylation of HBP1 by PRMT1 promotes tumor progression by regulating actin cytoskeleton remodeling