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STAPO: Stabilizing Reinforcement Learning for LLMs by Silencing Rare Spurious Tokens
Circulating Tumor Cells in Pancreatic Ductal Adenocarcinoma: The Systemic Execution Hub of Metastasis
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
Engineered immunosuppressive dendritic cells protect against cardiac remodelling
Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10346-5
Lesion-targeted immune modulation is a feasible strategy to control cardiac fibrosis, and engineered dendritic cells are a promising therapeutic platform for treating cardiac remodelling and heart failure.