Nature cancer最新文献_第8页

Development and validation of an autonomous artificial intelligence agent for clinical decision-making in oncology 用于肿瘤学临床决策的自主人工智能代理的开发和验证。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-06-06 DOI: 10.1038/s43018-025-00991-6

Dyke Ferber, Omar S. M. El Nahhas, Georg Wölflein, Isabella C. Wiest, Jan Clusmann, Marie-Elisabeth Leßmann, Sebastian Foersch, Jacqueline Lammert, Maximilian Tschochohei, Dirk Jäger, Manuel Salto-Tellez, Nikolaus Schultz, Daniel Truhn, Jakob Nikolas Kather

{"title":"Development and validation of an autonomous artificial intelligence agent for clinical decision-making in oncology","authors":"Dyke Ferber, Omar S. M. El Nahhas, Georg Wölflein, Isabella C. Wiest, Jan Clusmann, Marie-Elisabeth Leßmann, Sebastian Foersch, Jacqueline Lammert, Maximilian Tschochohei, Dirk Jäger, Manuel Salto-Tellez, Nikolaus Schultz, Daniel Truhn, Jakob Nikolas Kather","doi":"10.1038/s43018-025-00991-6","DOIUrl":"10.1038/s43018-025-00991-6","url":null,"abstract":"Clinical decision-making in oncology is complex, requiring the integration of multimodal data and multidomain expertise. We developed and evaluated an autonomous clinical artificial intelligence (AI) agent leveraging GPT-4 with multimodal precision oncology tools to support personalized clinical decision-making. The system incorporates vision transformers for detecting microsatellite instability and KRAS and BRAF mutations from histopathology slides, MedSAM for radiological image segmentation and web-based search tools such as OncoKB, PubMed and Google. Evaluated on 20 realistic multimodal patient cases, the AI agent autonomously used appropriate tools with 87.5% accuracy, reached correct clinical conclusions in 91.0% of cases and accurately cited relevant oncology guidelines 75.5% of the time. Compared to GPT-4 alone, the integrated AI agent drastically improved decision-making accuracy from 30.3% to 87.2%. These findings demonstrate that integrating language models with precision oncology and search tools substantially enhances clinical accuracy, establishing a robust foundation for deploying AI-driven personalized oncology support systems. Ferber et al. present an autonomous artificial intelligence agent system for deployment of specialized medical oncology computational tools, validating their system across various clinical scenarios representative of typical patient care workflows.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 8","pages":"1337-1349"},"PeriodicalIF":28.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Profiling platform-independent tumor classification using artificial intelligence 利用人工智能分析平台独立的肿瘤分类。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-06-06 DOI: 10.1038/s43018-025-00971-w

Claudia Manzl, Adelheid Woehrer

引用次数: 0

The current and emerging immunotherapy paradigm in small-cell lung cancer 当前和新兴的小细胞肺癌免疫治疗模式。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-06-05 DOI: 10.1038/s43018-025-00992-5

Kang Qin, Carl M. Gay, Lauren A. Byers, Jianjun Zhang

引用次数: 0

RIOK1 phase separation restricts PTEN translation via stress granules activating tumor growth in hepatocellular carcinoma RIOK1相分离通过应激颗粒激活肝癌肿瘤生长限制PTEN翻译。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-06-04 DOI: 10.1038/s43018-025-00984-5

Fanzheng Meng, Hairui Li, Yabin Huang, Chunxu Wang, Yufeng Liu, Chunting Zhang, Danlei Chen, Taofei Zeng, Shenyu Zhang, Yunyun Li, Bo Zhang, Chuandong Lang, Jie Xia, Wanxiang Xiong, Shixiang Pan, Xuedan Sun, Rick F. Thorne, Yao Liu, Jiabei Wang, Shugeng Zhang, Ruipeng Song, Jizhou Wang, Lianxin Liu

{"title":"RIOK1 phase separation restricts PTEN translation via stress granules activating tumor growth in hepatocellular carcinoma","authors":"Fanzheng Meng, Hairui Li, Yabin Huang, Chunxu Wang, Yufeng Liu, Chunting Zhang, Danlei Chen, Taofei Zeng, Shenyu Zhang, Yunyun Li, Bo Zhang, Chuandong Lang, Jie Xia, Wanxiang Xiong, Shixiang Pan, Xuedan Sun, Rick F. Thorne, Yao Liu, Jiabei Wang, Shugeng Zhang, Ruipeng Song, Jizhou Wang, Lianxin Liu","doi":"10.1038/s43018-025-00984-5","DOIUrl":"10.1038/s43018-025-00984-5","url":null,"abstract":"Resistance to tyrosine kinase inhibitors (TKIs) dampens their clinical efficacy in hepatocellular carcinoma (HCC). Stress granules formed by phase separation are essential to stress response and can be involved in therapy resistance, but their mechanisms in HCC are unclear. Here our screen shows that the atypical serine/threonine kinase RIOK1 is highly expressed in HCC, linked to poor prognosis, and transcriptionally activated by NRF2 under various stress conditions. RIOK1 undergoes liquid–liquid phase separation by incorporating IGF2BP1 and G3BP1 into stress granules that sequestrate PTEN messenger RNA reducing its translation. This process activates the pentose phosphate pathway, facilitating stress resolution and cytoprotection against TKI. We further show that the small-molecule inhibitor chidamide downregulates RIOK1 and enhances TKI efficacy. RIOK1-positive stress granules are found in donafenib-resistant tumors from patients with HCC. These findings reveal a link between stress granule dynamics, metabolic reprogramming and HCC progression, offering the potential means to improve TKI efficacy. Meng et al. demonstrate that RIOK1 phase separation leads to PTEN mRNA sequestration and pentose pathway activation resolving cellular stress in hepatocellular carcinoma. Targeting RIOK1 enhances response to tyrosine kinase inhibitors.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 7","pages":"1223-1241"},"PeriodicalIF":28.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stress granules shape metabolic reprogramming and drug resistance 应激颗粒形成代谢重编程和耐药性。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-06-04 DOI: 10.1038/s43018-024-00886-y

Shanshan Zhong, Huiyong Yin

引用次数: 0

TRMT6-mediated tRNA m1A modification acts as a translational checkpoint of histone synthesis and facilitates colorectal cancer progression trmt6介导的tRNA m1A修饰作为组蛋白合成的翻译检查点，促进结直肠癌的进展。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-06-03 DOI: 10.1038/s43018-025-00977-4

En-Wei Tao, Ye Wang, Juan Tan, Yan Chen, Tian-Yue Sun, Yu Hao, Hao-Lian Wang, Qianqian Liu, Yun-Qian Wang, Linna Fu, Zhi-Qing Zhan, Haoyan Chen, Jie Hong, Qin-Yan Gao, Jing-Yuan Fang, Ying-Xuan Chen

{"title":"TRMT6-mediated tRNA m1A modification acts as a translational checkpoint of histone synthesis and facilitates colorectal cancer progression","authors":"En-Wei Tao, Ye Wang, Juan Tan, Yan Chen, Tian-Yue Sun, Yu Hao, Hao-Lian Wang, Qianqian Liu, Yun-Qian Wang, Linna Fu, Zhi-Qing Zhan, Haoyan Chen, Jie Hong, Qin-Yan Gao, Jing-Yuan Fang, Ying-Xuan Chen","doi":"10.1038/s43018-025-00977-4","DOIUrl":"10.1038/s43018-025-00977-4","url":null,"abstract":"Transfer RNA modifications have emerged as critical regulators of translational reprogramming, yet their roles in colorectal cancer (CRC) remain largely elusive. Here, we find that tRNA N1-methyladenosine (m1A) methyltransferase TRMT6 is upregulated in human CRC tissues and high TRMT6 expression correlates with poor survival in patients with CRC. Using orthotopic, metastatic and conditional knockout mouse models, we establish the oncogenic role of TRMT6 in CRC. Mechanistically, TRMT6 increases tRNA m1A levels by maintaining the stability of the TRMT6–TRMT61A complex. Targeting TRMT6-mediated tRNA m1A modification in CRC cells destabilizes tRNA-Lys-TTT-1-1 and impairs histone mRNA translation in a codon-biased manner, thereby restricting histone synthesis and hindering cell cycle progression. Our study provides evidence that TRMT6 functions as a translational checkpoint in the accelerated histone synthesis of CRC cells, highlighting TRMT6 as a promising target for potential anti-CRC therapies. Tao et al. study the role of TRMT6 in colorectal cancer, where it is upregulated and show that TRMT6 supports histone biosynthesis by stabilizing tRNA-Lys-TTT-1-1. Targeting TRMT6 reduced histone mRNA translation in a codon-biased manner.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 8","pages":"1458-1476"},"PeriodicalIF":28.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glioblastoma shift from bulk to infiltrative growth is guided by plexin-B2-mediated microglia alignment in invasive niches 胶质母细胞瘤在侵袭性壁龛中由丛蛋白b2介导的小胶质细胞排列引导从块状向浸润性生长的转变。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-05-29 DOI: 10.1038/s43018-025-00985-4

Sangjo Kang, Mary E. Ughetta, Jack Y. Zhang, Valerie J. Marallano, Anirudh Sattiraju, Theodore Hannah, Shalaka Wahane, Aarthi Ramakrishnan, Molly Estill, Nadejda M. Tsankova, Li Shen, Alexander M. Tsankov, Roland H. Friedel, Hongyan Zou

{"title":"Glioblastoma shift from bulk to infiltrative growth is guided by plexin-B2-mediated microglia alignment in invasive niches","authors":"Sangjo Kang, Mary E. Ughetta, Jack Y. Zhang, Valerie J. Marallano, Anirudh Sattiraju, Theodore Hannah, Shalaka Wahane, Aarthi Ramakrishnan, Molly Estill, Nadejda M. Tsankova, Li Shen, Alexander M. Tsankov, Roland H. Friedel, Hongyan Zou","doi":"10.1038/s43018-025-00985-4","DOIUrl":"10.1038/s43018-025-00985-4","url":null,"abstract":"Glioblastoma (GBM) lethality stems from uncontrolled growth and infiltration. Using an immunocompetent murine model, we mapped GBM invasion and tumor-associated microglia and macrophage (TAM) interactions. We show that microglia are mobilized ahead of invasion, transforming morphologically and functionally—first forming glial nets around tumor infiltrates and then organizing into ‘oncostreams’ guiding collective migration. Single-cell RNA sequencing revealed three distinct states for tumor cells and microglia, corresponding to invasive niches versus tumor bulk. The invasive patterns and niche-specific gene signatures of tumor cells and TAMs were validated in human GBMs. We further identified a critical role of plexin-B2 in TAMs for resolving cell collision, aligning GBM cells and restructuring the extracellular matrix. Plexin-B2 ablation in TAMs disrupted invasion tracks, shifting GBM growth from infiltrative to bulk expansion. Understanding niche-specific TAM mobilization and anatomical–functional invasion units opens new strategies to target GBM invasion. Kang et al. define distinct spatial niches within glioblastoma (GBM) tumors according to their infiltrative nature and report that glioma cells induce microglia and macrophage alignments through plexin-B2 signaling, sustaining the invasive behavior of GBM.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 9","pages":"1505-1523"},"PeriodicalIF":28.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiomyocyte-localized CCDC25 senses NET DNA to promote doxorubicin cardiotoxicity by activating autophagic flux 心肌细胞定位的CCDC25感知NET DNA，通过激活自噬通量来促进阿霉素心脏毒性。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-05-29 DOI: 10.1038/s43018-025-00988-1

Man Nie, Dexin Lei, Zhou Liu, Kuan Zeng, Xinyan Liang, Peng Huang, Yu Wang, Peng Sun, Hang Yang, Panpan Liu, Runcong Nie, Silan Huang, Erwei Song, Wenqi Jiang, Zhiming Li, Yanqi Yang, Yi Xia, Linbin Yang

{"title":"Cardiomyocyte-localized CCDC25 senses NET DNA to promote doxorubicin cardiotoxicity by activating autophagic flux","authors":"Man Nie, Dexin Lei, Zhou Liu, Kuan Zeng, Xinyan Liang, Peng Huang, Yu Wang, Peng Sun, Hang Yang, Panpan Liu, Runcong Nie, Silan Huang, Erwei Song, Wenqi Jiang, Zhiming Li, Yanqi Yang, Yi Xia, Linbin Yang","doi":"10.1038/s43018-025-00988-1","DOIUrl":"10.1038/s43018-025-00988-1","url":null,"abstract":"Cardiotoxicity restricts the clinical use of anthracyclines. Although recent evidence indicates that aberrant activation of the cytosolic DNA-sensing pathway mediates cardiotoxicity, the function of extracellular DNA remains unclear. Here we observe a substantial increase in circulating neutrophil extracellular trap (NET) DNA in individuals with lymphoma experiencing cardiotoxicity after anthracycline-containing treatment. Using mouse models and human organotypic myocardial slices, we demonstrate that doxorubicin induces HMGB1-dependent cardiac NET formation, thereby promoting cardiac remodeling and dysfunction. Mechanistically, extracellular NET DNA is recognized by the transmembrane protein CCDC25 on cardiomyocytes, and their cross-talk generates reactive oxygen species and activates autophagic flux, subsequently impairing cardiac function. Targeting CCDC25 significantly alleviates anthracycline cardiotoxicity and synergizes with the antitumor efficacy of doxorubicin in lymphoma and breast cancer models. Overall, our findings demonstrate a previously unrecognized role of NETs and CCDC25 in anthracycline cardiotoxicity and suggest that targeting CCDC25 could provide a dual therapeutic and cardioprotective advantage. Nie et al. show that myocardial CCDC25 detects doxorubicin-induced neutrophil extracellular trap DNA and activates reactive oxygen species production and autophagy, leading to cardiotoxicity. Targeting CCDC25 exerts a cardioprotective effect without impacting the antitumor activity of doxorubicin in lymphoma and breast cancer models.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 8","pages":"1400-1418"},"PeriodicalIF":28.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia 骨骼肌内皮功能障碍通过激活素A-PGC1α轴驱动癌症恶病质的进展。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-05-26 DOI: 10.1038/s43018-025-00975-6

Young-Mee Kim, Mark A. Sanborn, Shaluah Vijeth, Priyanka Gajwani, Xinge Wang, Dahee Jung, Tibor Valyi-Nagy, Sreeparna Chakraborty, Georgina Mancinelli, Peter T. Toth, Evan H. Phillips, Paul Grippo, Ameen A. Salahudeen, Jooman Park, Su Yeon Yeon, Vijayalakshmi Ananthanarayanan, Yuwei Jiang, Steve Seung-Young Lee, Klara Valyi-Nagy, Jalees Rehman

{"title":"Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia","authors":"Young-Mee Kim, Mark A. Sanborn, Shaluah Vijeth, Priyanka Gajwani, Xinge Wang, Dahee Jung, Tibor Valyi-Nagy, Sreeparna Chakraborty, Georgina Mancinelli, Peter T. Toth, Evan H. Phillips, Paul Grippo, Ameen A. Salahudeen, Jooman Park, Su Yeon Yeon, Vijayalakshmi Ananthanarayanan, Yuwei Jiang, Steve Seung-Young Lee, Klara Valyi-Nagy, Jalees Rehman","doi":"10.1038/s43018-025-00975-6","DOIUrl":"10.1038/s43018-025-00975-6","url":null,"abstract":"Cachexia is the wasting of skeletal muscle in cancer and is a major complication that impacts a person’s quality of life. We hypothesized that cachexia is mediated by dysfunction of the vascular system, which is essential for maintaining perfusion and tempering inappropriate immune responses. Using transparent tissue topography, we discovered that loss of muscle vascular density precedes muscle wasting in multiple complementary tumor models, including pancreatic adenocarcinoma, colon carcinoma, lung adenocarcinoma and melanoma models. We also observed that persons suffering from cancer cachexia exhibit substantial loss of muscle vascular density. As tumors progress, increased circulating activin A remotely suppresses the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) in the muscle endothelium, thus inducing vascular leakage. Restoring endothelial PGC1α activity preserved vascular density and muscle mass in tumor-bearing mice. Our study suggests that restoring muscle endothelial function could be a valuable therapeutic approach for cancer cachexia. Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during cancer progression.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 8","pages":"1350-1369"},"PeriodicalIF":28.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The diverse roles of the circadian clock in cancer 生物钟在癌症中的多种作用。

IF 28.5 1区医学

Nature cancer Pub Date : 2025-05-26 DOI: 10.1038/s43018-025-00981-8

Bridget M. Fortin, Alisa L. Mahieu, Rachel C. Fellows, Yi Kang, Amber N. Lewis, Aya S. Ead, Katja A. Lamia, Yin Cao, Nicholas R. Pannunzio, Selma Masri

引用次数: 0