Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10564-x
l-2-Hydroxyglutarate is identified as a legitimate physiological signalling metabolite, and control of its levels is essential for postnatal growth and survival and correct renal development and function.
Pharmacol Res. 2026 May 17:108253. doi: 10.1016/j.phrs.2026.108253. Online ahead of print.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) exemplifies early systemic dissemination, with circulating tumor cells (CTCs) at its core. We advance a unified conceptual framework that positions CTCs as the systemic execution hub of PDAC metastasis, dynamic entity that coordinates the metastatic cascade via four cardinal functions: Seeding, Adapting, Engineering, and Signaling. Integrating eco-evolutionary dynamics, this hub actively drives phenotypic selection, niche remodeling, and immune evasion, while providing real-time biologic intelligence through liquid biopsy. Robust clinical correlation has not yet translated into routine practice because of technical variability, biological complexity, and a lack of interventional evidence. We therefore propose an evidence-driven, phased roadmap: grounded in prospective clinical cohort data, progressing from immediate multi-center technical standardization and pragmatic trials, such as minimal residual disease (MRD)-triggered salvage therapy, to mid-term biomarker-driven adjuvant trials and long-term integration into multimodal liquid biopsy ecosystems, aimed at intercepting this execution hub. By reframing CTCs from correlative indicators to actionable therapeutic targets and dynamic sentinels, this framework charts a path toward transforming the management of this recalcitrant systemic disease.
PMID:42150733 | DOI:10.1016/j.phrs.2026.108253
Am J Surg Pathol. 2026 Jun 1;50(6):695-704. doi: 10.1097/PAS.0000000000002533. Epub 2026 Mar 13.
ABSTRACT
With the application of molecular techniques in pathologic diagnosis, several novel primary pulmonary epithelial tumors have been continuously discovered and classified under the WHO classification of thoracic tumors. Recently, a pulmonary tumor with NFATC2 :: NUTM2B fusion was first documented, but the spectrum of NFATC2::NUTM2 fusion variants and their associated pathologic features remains incompletely characterized. Coincidentally, we also found and described 6 primary pulmonary tumors harboring recurrent NFATC2::NUTM2A/E fusions through integrated genomic analysis. These patients, including 4 females and 2 males, with a median age of 53 years, presented with incidentally detected peripheral lung nodules composed of monotonous epithelioid cells arranged in cords, nests, and trabeculae within a prominent desmoplastic stroma. All tumors exhibited a consistent immunophenotype: CK5/6+/GATA3+/calponin+/EMA+/DOG1 (perinuclear dot-like staining)/p63-. High-throughput chromosome conformation capture (Hi-C) analysis showed the structural variation of NFATC2::NUTM2E in all 6 cases, whereas RNA sequencing detected the fusion transcripts in 5 cases ( NFATC2::NUTM2A , n=2; NFATC2::NUTM2E , n=3). Ultrastructural examination of 1 case suggested epithelial differentiation. All patients remained disease-free after complete resection (median follow-up: 24 mo; range: 9 to 41 mo). These findings define a novel primary pulmonary tumor entity driven by NFATC2::NUTM2 fusions, and characterized by a distinctive immunophenotype, expanding the spectrum of NUTM2 -associated neoplasms. Our study underscores the utility of multiomics approaches for characterizing rare neoplasms and provides a diagnostic framework for this entity.
PMID:41821426 | DOI:10.1097/PAS.0000000000002533
Am J Surg Pathol. 2026 Mar 13. doi: 10.1097/PAS.0000000000002533. Online ahead of print.
ABSTRACT
With the application of molecular techniques in pathologic diagnosis, several novel primary pulmonary epithelial tumors have been continuously discovered and classified under the WHO classification of thoracic tumors. Recently, a pulmonary tumor with NFATC2::NUTM2B fusion was first documented, but the spectrum of NFATC2::NUTM2 fusion variants and their associated pathologic features remains incompletely characterized. Coincidentally, we also found and described 6 primary pulmonary tumors harboring recurrent NFATC2::NUTM2A/E fusions through integrated genomic analysis. These patients, including 4 females and 2 males, with a median age of 53 years, presented with incidentally detected peripheral lung nodules composed of monotonous epithelioid cells arranged in cords, nests, and trabeculae within a prominent desmoplastic stroma. All tumors exhibited a consistent immunophenotype: CK5/6+/GATA3+/calponin+/EMA+/DOG1 (perinuclear dot-like staining)/p63-. High-throughput chromosome conformation capture (Hi-C) analysis showed the structural variation of NFATC2::NUTM2E in all 6 cases, whereas RNA sequencing detected the fusion transcripts in 5 cases (NFATC2::NUTM2A, n=2; NFATC2::NUTM2E, n=3). Ultrastructural examination of 1 case suggested epithelial differentiation. All patients remained disease-free after complete resection (median follow-up: 24 mo; range: 9 to 41 mo). These findings define a novel primary pulmonary tumor entity driven by NFATC2::NUTM2 fusions, and characterized by a distinctive immunophenotype, expanding the spectrum of NUTM2-associated neoplasms. Our study underscores the utility of multiomics approaches for characterizing rare neoplasms and provides a diagnostic framework for this entity.
PMID:41821426 | DOI:10.1097/PAS.0000000000002533
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