bims-enbcad Biomed News
on Engineering biology for causal discovery
Issue of 2026–01–04
eleven papers selected by
Xiao Qin, University of Oxford
  1. The Role of Gut Microbiota in Colorectal Cancer Pathogenesis: A Comprehensive Literature Review.
  2. Genotype-to-phenotype mapping of somatic clonal mosaicism via single-cell co-capture of DNA mutations and mRNA transcripts.
  3. Spatial omics at the forefront: emerging technologies, analytical innovations, and clinical applications.
  4. Interpretation, extrapolation and perturbation of single cells.
  5. The Role of Prostaglandins as Major Inflammatory Mediators in Colorectal Cancer.
  6. Adaptive plasticity in targeted therapy.
  7. Lynch Syndrome in Focus: A Multidisciplinary Review of Cancer Risk, Clinical Management, and Special Populations.
  8. Implementing Immunoscore in colorectal cancer: lessons from cohort studies, limitations and barriers to adoption.
  9. Guardians within: Cross-talk between the gut microbiome and host immune system.
  10. ApCAFs: spatial niches and therapeutic insights across cancers.
  11. Building confidence.
  1. Int J Mol Sci. 2025 Dec 09. pii: 11870. [Epub ahead of print]26(24):
    The Role of Gut Microbiota in Colorectal Cancer Pathogenesis: A Comprehensive Literature Review.
    Dan Nicolae Paduraru, Alexandru Cosmin Palcau, Valeriu Gabi Dinca, Diana Mihaela Ciuc, Alexandru Constantinescu.
      Colorectal cancer (CRC) represents a significant global health burden, ranking as the third most frequently diagnosed malignancy worldwide. Emerging evidence has established a compelling association between gut microbiota dysbiosis and CRC pathogenesis, revealing complex mechanisms through which specific bacterial communities modulate carcinogenesis. This comprehensive review synthesizes current knowledge on the mechanistic contributions of gut microbiota to CRC development, with particular emphasis on key pathogenic bacteria including Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli. We examine the molecular pathways through which these microorganisms promote tumorigenesis, including chronic inflammation induction, immune response modulation, metabolic reprogramming, and direct genotoxic effects. Furthermore, we discuss the therapeutic implications of microbiota-targeted interventions and the potential utility of microbial biomarkers for early CRC detection. Understanding the intricate host-microbiota interactions in CRC pathogenesis may facilitate the development of novel preventive strategies and therapeutic approaches for this devastating disease.
    Keywords:  carcinogenesis; colorectal cancer; dysbiosis; gut microbiota; inflammation; microbiome
    DOI:  https://doi.org/10.3390/ijms262411870
  2. Cancer Discov. 2025 Dec 31.
    Genotype-to-phenotype mapping of somatic clonal mosaicism via single-cell co-capture of DNA mutations and mRNA transcripts.
    Dennis J Yuan, John Zinno, Theo Botella, Dalia Dhingra, Shu Wang, Allegra G Hawkins, Ariel Swett, Jesus Sotelo, Ramya Raviram, Clayton Hughes, Catherine Potenski, Katharine D Godfrey, Kara M Ainsworth, Shuzhen Xu, Jianwen Que, Julian A Abrams, Akira Yokoyama, Nobuyuki Kakiuchi, Seishi Ogawa, Dan A Landau.
      Somatic mosaicism is pervasively observed in human aging, with clonal expansions of cells harboring mutations in recurrently mutated driver genes. Bulk sequencing of tissues captures mutation frequencies, but cannot reconstruct clonal architectures nor delineate how driver mutations impact cellular phenotypes. We developed single-cell Genotype-to-Phenotype sequencing (scG2P) for high-throughput, highly-multiplexed, joint capture of genotyping of mutation hotspots and mRNA markers. We applied scG2P to aged esophagus samples from six individuals and observed large numbers of clones with a single driver event, accompanied by rare clones with two driver mutations. NOTCH1 mutants dominate the clonal landscape and are linked to stunted epithelial differentiation, while TP53 mutants promote clonal expansion through both differentiation biases and increased cell cycling. Thus, joint single-cell highly multiplexed capture of somatic mutations and mRNA transcripts enables high resolution reconstruction of clonal architecture and associated phenotypes in solid tissue somatic mosaicism.
    DOI:  https://doi.org/10.1158/2159-8290.CD-24-0853
  3. Cancer Cell. 2025 Dec 31. pii: S1535-6108(25)00543-4. [Epub ahead of print]
    Spatial omics at the forefront: emerging technologies, analytical innovations, and clinical applications.
    Yunhe Liu, Yibo Dai, Linghua Wang.
      Spatial omics transforms our understanding of cancer by revealing how tumor cells and the microenvironment are organized, interact, and evolve within tissues. Here, we synthesize advances in spatial technologies that map tumor ecosystems with unprecedented fidelity. We highlighted analytical breakthroughs-including multimodal integration and emerging spatial foundation models-that resolve functional niches and spatial communities, converting spatial patterns into mechanistic insights. We summarize how spatially organized features, from immune hubs to microbiota and neural interfaces, shape tumor evolution and clinical outcomes. We then outline how spatial approaches illuminate precancer biology, metastatic adaptation, and therapy response. Bridging discovery and translation, we provide a practical roadmap for incorporating spatial readouts into clinically oriented study design. We conclude by discussing persistent challenges in standardization and scalability and how high-plex spatial discoveries may be distilled into scalable, AI-enabled, clinically deployable assays, positioning spatial omics as a cornerstone of next-generation predictive and precision oncology.
    Keywords:  AI; ML; TME; artificial intelligence; cell-cell interaction; cellular neighborhood; computational pathology; machine learning; molecular imaging; multi-omics; multimodal data integration; proteomics; spatial biomarkers; spatial heterogeneity; spatial niche; spatial omics; transcriptomics; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.ccell.2025.12.009
  4. Nat Rev Genet. 2026 Jan 02.
    Interpretation, extrapolation and perturbation of single cells.
    Daniel Dimitrov, Stefan Schrod, Martin Rohbeck, Oliver Stegle.
      Single-cell analyses have transitioned from descriptive atlasing towards inferring causal effects and mechanistic relationships that capture cellular logic. Technological advances and the growing scale of observational and interventional datasets have fuelled the development of machine learning methods aimed at identifying such dependencies and extrapolating perturbation effects. Here, we review and connect these approaches according to their modelling concepts (including representation learning, causal inference, mechanistic discovery, disentanglement and population tracing), underlying assumptions and downstream tasks. We propose a unifying ontology to guide practitioners in selecting the most suitable methods for a given biological question, with detailed technical descriptions provided in an online resource . Finally, we identify promising computational directions and underexplored data properties that could pave the way for future developments.
    DOI:  https://doi.org/10.1038/s41576-025-00920-4
  5. Int J Mol Sci. 2025 Dec 18. pii: 12191. [Epub ahead of print]26(24):
    The Role of Prostaglandins as Major Inflammatory Mediators in Colorectal Cancer.
    Mario Macia Guardado, Valentina Lutz, Markus Hengstschläger, Helmut Dolznig.
      Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality, with inflammation playing a pivotal role in its pathogenesis. Chronic inflammation in the intestine significantly increases the risk of CRC development. Main compounds participating in the inflammatory process are prostaglandins; bioactive lipids derived from arachidonic acid metabolism via the cyclooxygenase (COX) pathway. While it is well known that prostaglandin E2 (PGE2) promotes CRC tumorigenesis, other prostaglandins, such as PGD2, PGF2α, and prostacyclin (PGI2), remain relatively underexplored. These prostaglandins may exert distinct or opposing effects on CRC development, but the current understanding of their functions is limited. Additionally, the impact of prostaglandins on immune regulation and the tumor microenvironment, is far from being fully understood. Addressing these knowledge gaps is crucial for identifying novel therapeutic targets and optimizing chemoprevention strategies. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of CRC, largely by inhibiting prostaglandin producing enzymes. However, their use is limited due to their gastrointestinal and cardiovascular side effects. Therefore, understanding the intricate role of inflammation and prostaglandin signaling in CRC is critical to develop safer and more effective chemopreventive approaches. This review summarizes the current knowledge of prostaglandins, linking inflammation and CRC. It further addresses the potential of targeting prostaglandin pathways for chemoprevention. Furthermore, we discuss emerging pharmacological targets that modulate prostaglandin production, signaling or degradation, offering promise for preventing CRC development.
    Keywords:  colorectal cancer; inflammation; microenvironment; prostaglandins
    DOI:  https://doi.org/10.3390/ijms262412191
  6. Cancer Cell. 2025 Dec 31. pii: S1535-6108(25)00541-0. [Epub ahead of print]
    Adaptive plasticity in targeted therapy.
    Vito Amodio, Giorgio Patelli, Alberto Bardelli.
      In this issue of Cancer Cell, Zhang et al. show that dual KRAS-EGFR inhibition induces a reversible Paneth-like transition in colorectal cancer, sustaining mitogen-activated protein kinase (MAPK) reactivation through a SMAD1-FGFR3 axis. This reinforces emerging evidence that lineage remodeling underlies early adaptive escape from targeted therapy and carries potential clinical relevance.
    DOI:  https://doi.org/10.1016/j.ccell.2025.12.007
  7. Cancers (Basel). 2025 Dec 13. pii: 3981. [Epub ahead of print]17(24):
    Lynch Syndrome in Focus: A Multidisciplinary Review of Cancer Risk, Clinical Management, and Special Populations.
    Seyma Eroglu, Ilhan Birsenogul, Alexandra P Bowen, Joseph F Doyle, Stephen E Pupkin, Joaquin Villar, Christopher M Tarney, Edwin Gandia, Danielle M Pastor, Juvianee I Estrada-Veras.
      Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary cancer syndrome significantly increasing the risk of colorectal cancer (CRC) and various extracolonic cancers, including endometrial, ovarian, and gastric cancers. LS results from germline pathogenic variants (GPVs) in DNA mismatch repair (MMR) genes, such as MLH1, MSH2, MSH6, and PMS2, leading to microsatellite instability (MSI). This review explores the multifaceted aspects of LS, covering clinical presentation, genetic underpinnings, and emerging therapeutic strategies. The discussion explores the importance of identifying at-risk individuals, facilitating personalized cancer surveillance and prevention strategies. Molecular insights into distinguishing between sporadic and LS-associated cancers are also examined, with a focus on somatic testing methods, including MSI and immunohistochemistry (IHC). The gynecological cancer risks, particularly those related to endometrial and ovarian malignancies, are addressed, underscoring the need for early detection and risk-reducing interventions. Recent advancements in the management of colorectal and other LS-related cancers are highlighted, with particular attention to the growing role of immunotherapy, including immune checkpoint inhibitors, and immunoprevention strategies. With ongoing advances in our understanding of LS, opportunities for earlier detection, more effective prevention, and innovative treatments continue to expand. This narrative review adopts a multidisciplinary approach to provide a comprehensive understanding of LS, from its genetic basis to current clinical and therapeutic practices, with the ultimate goal of improving patient outcomes and enhancing the quality of care.
    Keywords:  Lynch syndrome; Lynch-like syndrome; cancer genetics; cancer surveillance; immunotherapy; microsatellite instability; mismatch repair genes; molecular diagnostics; risk-reduction strategies
    DOI:  https://doi.org/10.3390/cancers17243981
  8. J Pathol Clin Res. 2026 Jan;12(1): e70071
    Implementing Immunoscore in colorectal cancer: lessons from cohort studies, limitations and barriers to adoption.
    Matthew Ss Hsu, Suet Yi Leung.
      The Immunoscore (IS) quantifies the immune contexture of colorectal cancer (CRC) by measuring CD3+ and CD8+ T-cell densities in the tumour centre and invasive margin, providing superior prognostic performance compared with TNM staging and mismatch-repair (MMR) status alone. Large international cohort studies have validated its ability to predict benefit from adjuvant chemotherapy in stage III colon cancer. More recently, Immunoscore-IC - a refined version that incorporates PD-L1+ cell density and spatial interactions - has emerged as the first biomarker capable of identifying the subset of patients with proficient-MMR (pMMR/MSS) metastatic CRC who derive significant benefit from immune checkpoint inhibitors. Despite these advances, technical requirements, biological limitations, and reliance on retrospective data continue to hinder widespread clinical adoption. Addressing some of these challenges could enhance its utility and facilitate broader integration into routine pathology practice. In this commentary, we place landmark IS publications within the evolving research landscape, including papers published in The Journal of Pathology Clinical Research; integrate findings from recent international validation cohorts and adjuvant trials; and highlight the growing evidence supporting IS as a robust prognostic tool with clear predictive implications for both chemotherapy and immunotherapy in CRC.
    Keywords:  Immunoscore; colon; colon cancer; digital image analysis; digital pathology; immunohistochemistry; immunology
    DOI:  https://doi.org/10.1002/2056-4538.70071
  9. World J Gastrointest Pathophysiol. 2025 Dec 22. 16(4): 111245
    Guardians within: Cross-talk between the gut microbiome and host immune system.
    Nabanita Ghosh, Krishnendu Sinha.
      The gut microbiome, a complex ecosystem of trillions of microorganisms, plays a crucial role in immune system regulation and overall health. This review explores the intricate cross-talk between the gut microbiota and the host immune system, emphasizing how microbial communities shape immune cell differentiation, modulate inflammatory responses, and contribute to immune homeostasis. Key interactions between innate and adaptive immune cells - including macrophages, dendritic cells, natural killer cells, innate Lymphoid cells, T cells, and B cells - and gut microbiota-derived metabolites such as short-chain fatty acids are discussed. The role of commensal bacteria in neonatal immune system development, mucosal barrier integrity, and systemic immunity is highlighted, along with implications for autoimmune diseases, inflammatory conditions, and cancer immunotherapy. Recent advances in metagenomics, metabolomics, and single-cell sequencing have provided deeper insights into the microbiota-immune axis, opening new avenues for microbiome-based therapeutic strategies. Understanding these interactions paves the way for novel interventions targeting immune-mediated diseases and optimizing health through microbiome modulation.
    Keywords:  Dysbiosis; Gut microbiome; Immune system; Inflammation; Microbiota-immune axis
    DOI:  https://doi.org/10.4291/wjgp.v16.i4.111245
  10. Trends Cancer. 2025 Dec 30. pii: S2405-8033(25)00312-7. [Epub ahead of print]
    ApCAFs: spatial niches and therapeutic insights across cancers.
    Wenlong Li, Gideon Nsubuga, Giulia Biffi.
      Although interest in antigen-presenting cancer-associated fibroblasts (apCAFs) is increasing, their therapeutic potential remains poorly understood. In a recent study, Chen et al. reveal two osteopontin-expressing apCAF populations present across malignancies and distinct in origin and location: mesothelial-like (M-)apCAFs, which are found near cancer cells, and fibrocyte-like (F-)apCAFs, which associate with lymphocyte-enriched niches.
    Keywords:  Antigen-presenting cancer-associated fibroblasts; fibrocytes; mesothelial cells; spatial niches
    DOI:  https://doi.org/10.1016/j.trecan.2025.12.005
  11. Science. 2026 Jan;391(6780): 102
    Building confidence.
    Zheng Liu.
      
    DOI:  https://doi.org/10.1126/science.aee9318
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