Reading view
Understanding Prompt Management in GitHub Repositories: A Call for Best Practices
MetaVoxel: Joint Diffusion Modeling of Imaging and Clinical Metadata
High-Throughput Dissection of Inter-Organ Genetic Networks: A Multi-Omic Systems Biology Approach
SLAS Technol. 2025 Dec 11:100376. doi: 10.1016/j.slast.2025.100376. Online ahead of print.
ABSTRACT
The existing multi-omic analyses are frequently confined to individual tissues, and the regulatory picture of the systemic regulator of complex physiology and disease is hidden. To fill this gap, we have created a unified systems biology model of the high-throughput dissection of inter-organ genetic networks. Our model incorporates transcriptomic, epigenomic and proteomic analysis of five major organs (liver, kidney, heart, lung, brain) using the Multi-Omics Factor Analysis (MOFA+) tool, specifically, cross-tissue coordination. We characterized 27 evidence-heavy cross-tissue modules (FDR < 0.05) that are major hubs such as *HNF4Aenda NRF2cheng8loadmasterregulatingconstitutionembryonicstemcellularinfoncogenes recognize them. One notable observation was liver-kidney metabolic axis, significant cross-talks in hepatocyte organoids are confirmed with CRISPR knockdown, which suppresses the expression of transporters expressed by the kidney. Our work offers a scalable validated framework that goes beyond organ-centric perspectives, which can be used as a potent tool of systemic disease modelling and precision medicine.
PMID:41389879 | DOI:10.1016/j.slast.2025.100376
Mapping the inflammatory origins of lung cancer
Cancer Cell. 2025 Dec 11:S1535-6108(25)00498-2. doi: 10.1016/j.ccell.2025.11.005. Online ahead of print.
ABSTRACT
How early precursor cells and their surrounding microenvironment cooperate to drive oncogenic progression in lung adenocarcinoma (LUAD) remains elusive. In this issue of Cancer Cell, Peng et al. conducted multimodal spatial-omics to comprehensively profile precancerous lung and LUAD tissues, uncovering alveolar progenitors and proinflammatory niches that co-evolve during cancer progression.
PMID:41386222 | DOI:10.1016/j.ccell.2025.11.005
Minimal Residual Disease Detection: Bridging Molecular and Clinical Strategies for Recurrence Prevention in Gynecologic Cancers
Int J Mol Sci. 2025 Dec 3;26(23):11708. doi: 10.3390/ijms262311708.
ABSTRACT
Gynecologic cancers remain a major global health burden, particularly in low- and middle-income countries, with high incidence and mortality rates around 45-50%. The detection of minimal residual disease (MRD) is transforming the management of recurrence risk in gynecologic cancers through highly sensitive molecular technologies. MRD encompasses small populations of residual cancer cells or post-treatment molecular traces but remain undetectable by conventional methods. Its detection relies on circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and advanced next-generation sequencing (NGS), with ctDNA-based MRD assays having sensitivity levels between 85% and over 99%. Other technologies, such as liquid biopsies and digital PCR, are also in development. MRD status has demonstrated high predictors of recurrence and survival with positive MRD strongly associated with poor outcomes and negative MRD indicates sustained remission. However, MRD detection faces significant limitations, such as tumor heterogeneity, inconstant ctDNA levels, technical issues of false-negative results, and limited clinical accessibility. Therefore, this review presents current evidence regarding the molecular detection of MRD in gynecologic malignancies and assesses its prognostic and predictive relevance. Ultimately, MRD continuous integration into clinical practice offers a promising modality to enable early relapse detection, more precise therapeutic decision-making, and the improvement of personalized medicine access to gynecologic cancers worldwide.
PMID:41373852 | PMC:PMC12692091 | DOI:10.3390/ijms262311708
Macrophage-targeted immunocytokine leverages myeloid, T, and NK cell synergy for cancer immunotherapy
Pancreatic Cancer Organoids: Modeling Disease and Guiding Therapy
Cancers (Basel). 2025 Nov 30;17(23):3850. doi: 10.3390/cancers17233850.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. An unmet need exists for reliable biomarkers and in vitro models capable of predicting patient drug response to advance personalized medicine. Traditional models fail to represent the tumor's complexity and the role of the stromal environment in chemoresistance. Patient-derived organoids (PDOs) overcome these limitations, enabling multi-omics profiling and reliable drug testing for functional precision medicine. This review provides a comprehensive overview of PDAC PDO research, emphasizing the following major areas: (i) the genetic and phenotypic fidelity of PDOs, (ii) their predictive value for drug response and chemoresistance, (iii) the integration of the extracellular matrix and tumor microenvironment (TME) components, and (iv) emerging technologies. Studies confirm that PDOs faithfully represent the primary tumor's specific genetic features and retain intratumoral heterogeneity. PDO-based platforms have demonstrated a strong correlation between in vitro drug sensitivity and in vivo efficacy in xenograft models, validating their utility for identifying drug candidates, repurposing existing drugs, and determining effective combinations. Efforts are ongoing to integrate crucial TME components, like cancer-associated fibroblasts, using innovative co-culture platforms such as fused PDOs and InterOMaX, to better model desmoplasia and chemoresistance mechanisms. Furthermore, PDO technology is converging with microphysiological systems and artificial intelligence tools to facilitate high-throughput drug screening and dynamic, real-time monitoring of therapeutic effects. The integration of PDOs into biobanks and advanced screening platforms holds the potential to accelerate drug discovery and improve therapeutic outcomes for PDAC patients, if challenges related to protocol standardization and regulatory acceptance are addressed.
PMID:41375051 | PMC:PMC12690986 | DOI:10.3390/cancers17233850
AI-driven virtual cell models in preclinical research: technical pathways, validation mechanisms, and clinical translation potential
npj Digital Medicine, Published online: 11 December 2025; doi:10.1038/s41746-025-02198-6
AI-driven virtual cell models in preclinical research: technical pathways, validation mechanisms, and clinical translation potential