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  1. 2시간 전

    356-The LINUXtrial: AI Enhances Precision Treatment

    The LINUX trial investigated the effectiveness of using artificial intelligence to guide precision medicine for patients with advanced HR+/HER2– breast cancer who failed initial treatments. By utilizing digital pathology and deep learning to analyze tumor images, researchers categorized patients into four distinct molecular subtypes (SNF1–4) without the high cost of traditional genomic sequencing. Each group received a specific targeted therapy tailored to their subtype’s unique biological characteristics or a standard treatment chosen by their doctor. The study found that this AI-assisted subtyping significantly improved response rates and survival outcomes, particularly for the SNF2 and SNF4 groups. While some experimental regimens were more successful than others, the overall results demonstrate that personalized treatment strategies can outperform traditional "one-size-fits-all" chemotherapy. These findings suggest a scalable way to integrate machine learning into clinical oncology to enhance patient care and therapeutic efficacy.References: Fan L, Zhang W J, Li H P, et al. Precision treatment with artificial intelligence assisted subtyping enhances therapeutic efficacy in HR+/HER2− breast cancer: The LINUXtrial[J]. Cancer Cell, 2025.

    15분

  2. 9시간 전

    355-Paneth-like Transition Drives Cancer Resistance

    This research identifies a Paneth-like cell transition as a primary driver of non-genetic resistance to combined KRAS and EGFR inhibition in colorectal cancer (CRC). By utilizing genetically engineered mouse models and patient-derived organoids, the authors demonstrate that CRC cells adopt a secretory lineage state to evade therapeutic pressure and reactivate MAPK signaling. The study reveals that the SMAD1-FGFR3 signaling axis orchestrates this cellular plasticity and lineage switch. Importantly, the researchers found that pharmacological or genetic inhibition of FGFR3 effectively blocks this transition and restores drug sensitivity. These findings suggest that triple combination therapy—targeting KRAS, EGFR, and FGFR3—could prevent treatment relapse in patients with KRAS-mutant CRC. Evidence from clinical biopsies confirms that this Paneth-like enrichment is a conserved survival strategy in human patients undergoing targeted therapy.References: Zhang Y, Chen J, She Y, et al. Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer[J]. Cancer Cell, 2025.

    13분

  3. 1일 전

    354-Medulloblastoma Stem Cell Programs and Progression

    This research explores the molecular origins and progression of medulloblastoma, a highly aggressive pediatric brain cancer. While sequencing has defined four major molecular subgroups, current treatments fail to eliminate the stem and progenitor cells that drive tumor growth and drug resistance. The authors argue for the development of faithful human models, such as 3D organoids, to better mirror human-specific brain development compared to traditional mouse models. A significant focus is placed on the post-transcriptional landscape, suggesting that mechanisms like alternative splicing offer untapped opportunities for targeted therapies and biomarkers. Furthermore, the text addresses the critical need to understand metastatic spread, which remains the leading cause of mortality in these young patients. Ultimately, the sources advocate for shifting beyond data collection toward functional validation of oncogenic drivers to improve clinical outcomes.References: Zagozewski J, Haldipur P, Millen K J, et al. Medulloblastoma stem cell programs: Molecular roadmaps of disease progression[J]. Developmental Cell, 2025.

    18분

  4. 1일 전

    353-IL-36γ Armored CAR T Cells Reprogram Neutrophils

    The research article describes a breakthrough in solid tumor immunotherapy using IL-36γ armored CAR T cells. While traditional CAR T therapies often struggle with antigen heterogeneity and the immunosuppressive tumor microenvironment, this study demonstrates that secreting the pro-inflammatory cytokine IL-36γ allows CAR T cells to effectively eradicate tumors. The primary mechanism involves reprogramming neutrophils into a specialized subset that possesses both tumoricidal activity and antigen-presenting capabilities. These "educated" neutrophils activate the host's own immune system, triggering epitope spreading and the expansion of endogenous T cells that target various tumor antigens. Remarkably, this treatment achieves durable results and long-term immunity without the need for traditional lymphodepleting chemotherapy. Consequently, this strategy offers a promising method for overcoming the biological barriers that typically limit adoptive cell therapies in solid malignancies.References: Zuo Y, Vohwinkel D J, Dong B, et al. IL-36γ armored CAR T cells reprogram neutrophils to induce endogenous antitumor immunity[J]. Cancer Cell, 2025.

    14분

  5. 2일 전

    352-Multi-omic Landscape of Human Gliomas

    This research presents a comprehensive spatial multi-omic atlas of human gliomas, mapping the complex landscape of these lethal brain tumors from initial diagnosis through recurrence. By integrating proteomic, transcriptomic, and glycomic data from 310 patients, the study identifies critical factors that contribute to the failure of current targeted therapies and immunotherapies. A major finding reveals that tumor antigen variability, such as inconsistent B7H3 and EGFR expression, prevents effective cancer cell targeting across diverse patient populations. Furthermore, the analysis demonstrates that while N-glycosylation patterns serve as the most accurate indicators of tumor grade, the immune molecular landscape is the strongest predictor of patient survival. The researchers discovered that tumor recurrence is driven by a spatial reorganization of the microenvironment, shifting toward immunosuppressive myeloid niches. This study provides an open-source data repository intended to serve as a foundational resource for refining tumor classification and designing more effective clinical interventions.References: Piyadasa H, Oberlton B, Ribi M, et al. Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence[J]. Cancer Cell, 2025.

    16분

  6. 2일 전

    351-RHOA Regulates Mitochondria-ER Contact Sites

    This article identifies the small GTPase RHOA as a critical controller of mitochondria-endoplasmic reticulum contact sites (MERCS). Through a genome-wide screen, scientists discovered that RHOA facilitates organelle communication by directly binding to the ER protein VAPB, which stabilizes its interaction with the mitochondrial protein PTPIP51. The study demonstrates that manipulating RHOA levels—either through its degradation via the CUL3 pathway or through pharmacological means—directly impacts essential functions like calcium transfer and metabolic remodeling. Furthermore, the authors reveal that disease-related mutations in these proteins disrupt this tethering mechanism, potentially contributing to cancer, hypertension, and neurodegenerative disorders like ALS. Ultimately, the findings establish RHOA as a molecular switch that tunes inter-organellar proximity, offering new insights into cellular health and potential therapeutic targets.References: Yang Z, Nakajima S, Chen H, et al. RHOA regulates mitochondria-ER contact sites through modulation of the VAPB/PTPIP51 tether[J]. Nature Communications, 2025.

    14분

  7. 3일 전

    350-PhenoProfiler: Image-Based Drug Discovery Learning

    The paper introduces PhenoProfiler, a sophisticated deep learning framework designed to revolutionize image-based drug discovery by analyzing how cells respond to chemical treatments. Unlike traditional methods that require complex preprocessing and image segmentation, this end-to-end system directly converts high-content microscopy images into compact, biologically meaningful representations. The model utilizes a unique multi-objective learning strategy—combining classification, regression, and contrastive learning—to ensure high accuracy and robustness against technical noise. Extensive testing on hundreds of thousands of images proves that PhenoProfiler significantly outperforms existing tools in identifying drug mechanisms and generalizing across different cell lines. Furthermore, its specialized phenotype correction strategy enhances the detection of subtle biological signals, making it a scalable solution for AI-driven pharmaceutical research. This innovation facilitates a more precise, interpretable understanding of cellular behavior to accelerate the identification of new therapeutic targets.References: Li B, Zhang B, Zhang C, et al. PhenoProfiler: advancing phenotypic learning for image-based drug discovery[J]. Nature Communications, 2025.

    17분

  8. 3일 전

    349-Spatial organization of mitochondria in neurons

    This research utilizes large-scale electron microscopy datasets to establish quantitative rules governing the morphology and spatial positioning of mitochondria within neural circuits. By analyzing thousands of neurons in both Drosophila and mice, researchers discovered that mitochondrial shapes are so cell-type specific they can act as "fingerprints" to identify specific neurons and neurotransmitter identities. The study demonstrates that these organelles are positioned with high precision relative to synapses and branch points, with their distribution correlating strongly to regional brain activity. In the fly's mushroom body, mitochondrial presence varies across functional compartments, suggesting that cells strategically allocate metabolic resources to support specific synaptic connections. Ultimately, these findings reveal that mitochondria are not merely generic powerhouses but are precisely organized components that link subcellular architecture to broader brain connectivity and function.References: Sager G, Pfeiffer P, Wu H, et al. Spatial and morphological organization of mitochondria in neurons across a connectome[J]. Science, 2025: eads6674.

    16분
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Sharing research articles, tracking the latest developments

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    2025년 - 2026년
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