Cancer research最新文献_第3页

Paving a Path to Clinical Impact with Radiomics: Enabling Reproducibility and Reach 为放射组学的临床影响铺平道路：实现可重复性和可及性

IF 11.2 1区医学

Cancer research Pub Date : 2025-07-02 DOI: 10.1158/0008-5472.can-25-2083

Mohamad El-Jammal, Caroline Chung

{"title":"Paving a Path to Clinical Impact with Radiomics: Enabling Reproducibility and Reach","authors":"Mohamad El-Jammal, Caroline Chung","doi":"10.1158/0008-5472.can-25-2083","DOIUrl":"https://doi.org/10.1158/0008-5472.can-25-2083","url":null,"abstract":"Radiomics, the extraction of quantitative data from images, holds promise for noninvasively characterizing tumor phenotypes. Tools like LIFEx have improved the accessibility, transparency, and reproducibility of radiomic feature extraction by offering standardized, user-friendly workflows across imaging modalities. Introduction of such a platform that enables consistent and transparent analytics has helped democratize access to the exploration of radiomics and has highlighted other fundamental challenges in radiomics, addressing upstream heterogeneity in image acquisition, reconstruction, and region-of-interest segmentation that impede reproducibility. Differences in these upstream steps can drastically alter radiomic features, even when downstream processing is standardized. We highlight ongoing efforts and fundamental challenges that the community will need to tackle collectively to enable the clinical translation of radiomics. By addressing variability throughout the radiomic pipeline, we can ensure that radiomic features better reflect tumor biology, as well as fulfill their potential as robust, generalizable biomarkers for precision oncology. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI. See related article by Nioche and colleagues, Cancer Res 2018;78:4786-89","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"15 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533086","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

Illuminating the Noncoding Genome in Cancer Using Artificial Intelligence. 利用人工智能阐明癌症中的非编码基因组。

IF 12.5 1区医学

Cancer research Pub Date : 2025-07-02 DOI: 10.1158/0008-5472.CAN-25-0482

Maria Del Mar Alvarez-Torres, Xi Fu, Raul Rabadan

引用次数: 0

Informatics at the Frontier of Cancer Research 癌症研究前沿的信息学

IF 11.2 1区医学

Cancer research Pub Date : 2025-07-02 DOI: 10.1158/0008-5472.can-24-2829

Kathleen Noller, Taxiarchis Botsis, Pablo G. Camara, Lauren Ciotti, Lee AD. Cooper, Jeremy Goecks, Malachi Griffith, Brian J. Haas, Trey Ideker, Rachel Karchin, Despina Kontos, Jiaying Lai, Daniel Marcus, Clifford A. Meyer, Kristen Naegle, Sarthak Pati, Bjoern Peters, Dexter Pratt, Benjamin J. Raphael, Michael Reich, Guergana K. Savova, Carrie Wright, Elana J. Fertig, Spyridon Bakas

引用次数: 0

Artificial Intelligence–Driven Cancer Diagnostics: Enhancing Radiology and Pathology through Reproducibility, Explainability, and Multimodality 人工智能驱动的癌症诊断：通过可重复性、可解释性和多模态增强放射学和病理学

IF 11.2 1区医学

Cancer research Pub Date : 2025-07-02 DOI: 10.1158/0008-5472.can-24-3630

Pegah Khosravi, Thomas J. Fuchs, David Joon Ho

{"title":"Artificial Intelligence–Driven Cancer Diagnostics: Enhancing Radiology and Pathology through Reproducibility, Explainability, and Multimodality","authors":"Pegah Khosravi, Thomas J. Fuchs, David Joon Ho","doi":"10.1158/0008-5472.can-24-3630","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-3630","url":null,"abstract":"The integration of artificial intelligence (AI) in cancer research has significantly advanced radiology, pathology, and multimodal approaches, offering unprecedented capabilities in image analysis, diagnosis, and treatment planning. AI techniques provide standardized assistance to clinicians, in which many diagnostic and predictive tasks are manually conducted, causing low reproducibility. These AI methods can additionally provide explainability to help clinicians make the best decisions for patient care. This review explores state-of-the-art AI methods, focusing on their application in image classification, image segmentation, multiple instance learning, generative models, and self-supervised learning. In radiology, AI enhances tumor detection, diagnosis, and treatment planning through advanced imaging modalities and real-time applications. In pathology, AI-driven image analysis improves cancer detection, biomarker discovery, and diagnostic consistency. Multimodal AI approaches can integrate data from radiology, pathology, and genomics to provide comprehensive diagnostic insights. Emerging trends, challenges, and future directions in AI-driven cancer research are discussed, emphasizing the transformative potential of these technologies in improving patient outcomes and advancing cancer care. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"65 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533043","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

Cancer Research in the Age of Big Data. 大数据时代的癌症研究。

IF 11.2 1区医学

Cancer research Pub Date : 2025-07-02 DOI: 10.1158/0008-5472.can-25-2201

Christine A Iacobuzio-Donahue

引用次数: 0

Leveraging Whole-Exome Sequencing and Mutational Signatures to Detect Homologous Recombination Deficiency in Cancer. 利用全外显子组测序和突变特征检测癌症同源重组缺陷。

IF 11.2 1区医学

Cancer research Pub Date : 2025-07-02 DOI: 10.1158/0008-5472.can-25-2105

Joonoh Lim,Young Seok Ju

{"title":"Leveraging Whole-Exome Sequencing and Mutational Signatures to Detect Homologous Recombination Deficiency in Cancer.","authors":"Joonoh Lim,Young Seok Ju","doi":"10.1158/0008-5472.can-25-2105","DOIUrl":"https://doi.org/10.1158/0008-5472.can-25-2105","url":null,"abstract":"Homologous recombination is a high-fidelity DNA repair mechanism essential for maintaining genome stability. Impairment of this pathway, often due to BRCA1 or BRCA2 inactivation, leads to homologous recombination deficiency (HRD), forcing cells to rely on error-prone mechanisms for repairing DNA double-strand breaks, such as nonhomologous or microhomology-mediated end joining. HRD is a clinically important biomarker, particularly in breast and ovarian cancers, as it predicts responsiveness to platinum-based chemotherapies and PARP inhibitors. However, current tests in the clinical setting, mostly based on targeted panel sequencing, lack specificity and lead to a substantial number of false positives. In contrast, whole-genome sequencing, despite its high accuracy, remains largely confined to research because of high costs and logistical constraints. In this issue of Cancer Research, Abbasi and colleagues present HRProfiler, a machine learning-based tool that accurately detects HRD using whole-exome sequencing (WES) data, which is increasingly accessible in clinical oncology. Notably, it demonstrates improved sensitivity in the WES setting compared with existing tools, such as HRDetect and SigMA. As WES continues to gain traction, HRProfiler offers a promising step toward democratizing HRD detection and enabling more precise, genomics-guided treatment strategies. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI. See related article by Abbasi et al., p. 2504.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"8 1","pages":"2348-2350"},"PeriodicalIF":11.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533405","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

TRAF3IP2-AS1 Deficiency Induces Necroptosis to Promote Pancreatic Cancer Liver Metastasis TRAF3IP2-AS1缺失诱导坏死性下垂促进胰腺癌肝转移

IF 11.2 1区医学

Cancer research Pub Date : 2025-06-30 DOI: 10.1158/0008-5472.can-24-4784

Yong-Ding Wu, Xiao-Xiao Huang, Hao-Xiang Zhang, Yu Pan, Cheng-Ke Xie, Ge Li, Cai-Feng Lin, Xin-Quan Lin, Zhi-Yuan Li, Yin-Hao Chen, Jian-Fei Hu, Hong-Yi Lin, Shun-Cang Zhu, Zu-Wei Wang, Yi-Feng Tian, Qiao-Wei Li, Cheng-Yu Liao, Shi Chen

{"title":"TRAF3IP2-AS1 Deficiency Induces Necroptosis to Promote Pancreatic Cancer Liver Metastasis","authors":"Yong-Ding Wu, Xiao-Xiao Huang, Hao-Xiang Zhang, Yu Pan, Cheng-Ke Xie, Ge Li, Cai-Feng Lin, Xin-Quan Lin, Zhi-Yuan Li, Yin-Hao Chen, Jian-Fei Hu, Hong-Yi Lin, Shun-Cang Zhu, Zu-Wei Wang, Yi-Feng Tian, Qiao-Wei Li, Cheng-Yu Liao, Shi Chen","doi":"10.1158/0008-5472.can-24-4784","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-4784","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies. PDAC is characterized by prominent necrotic foci within the tumor and a high propensity for distant liver metastasis, leading to poor prognosis. Here, using patient-derived organoid models, single-cell RNA sequencing and multiplex immunofluorescence staining of PDAC patient samples, in vivo TGFβ1 conditional knockout mouse models, and 3D in vitro models, we discovered that the formation of intratumoral necrotic foci in pancreatic cancer is closely associated with liver metastatic events. This process was triggered by deficiency of the lncRNA TRAF3IP2-AS1 that induced necroptosis, which was accompanied by an immunosuppressive microenvironment. Mechanistically, TRAF3IP2-AS1 blocked necroptosis by reducing the mRNA stability of MLKL through competitively binding to IGF2BP2. Loss of TRAF3IP2-AS1 also promoted necroptosis by promoting RIPK3 phosphorylation via interference with the ubiquitination of the phosphatase PPM1B that dephosphorylates RIPK3. Additionally, TRAF3IP2-AS1 deficiency promoted the release of TGFβ1 from tumor cells, which induced an M2-like immunosuppressive phenotype and the release of more TGFβ1. The elevated production of TGFβ1 created a feedback loop that promoted the transcription of TRAF3IP2-AS1 in tumor cells to balance necroptosis. Overall, these findings identify TRAF3IP2-AS1 as a key regulator of necroptosis and the formation of an immunosuppressive microenvironment in PDAC, providing potential therapeutic targets for treating liver metastasis in patients with pancreatic cancer.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"27 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520637","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

Bone voyage: OPN's path from skeleton to systemic immunosuppression 骨之旅：OPN从骨骼到全身免疫抑制的路径

IF 11.2 1区医学

Cancer research Pub Date : 2025-06-30 DOI: 10.1158/0008-5472.can-25-2702

Kyoko Hashimoto, Kazuo Okamoto, Hiroshi Takayanagi

{"title":"Bone voyage: OPN's path from skeleton to systemic immunosuppression","authors":"Kyoko Hashimoto, Kazuo Okamoto, Hiroshi Takayanagi","doi":"10.1158/0008-5472.can-25-2702","DOIUrl":"https://doi.org/10.1158/0008-5472.can-25-2702","url":null,"abstract":"Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment across multiple tumor types. However, some patients receive limited benefit, and the underlying mechanisms of resistance remain a formidable challenge, spurring intensive research efforts. A recent study published in Cancer Cell reveals that bone metastases actively suppress systemic anti-tumor immunity and contribute to ICB resistance. Analysis of clinical cohorts showed that patients with bone metastases exhibit reduced responsiveness to ICBs. Mechanistically, the study demonstrated that intraosseous tumors enhance osteopontin (OPN) production by osteoclasts. Circulating OPN was found to impair differentiation of progenitor exhausted T cells (Tpex), a subset correlated with ICB responsiveness, in distant tumor sites, thereby blunting anti-tumor immune response. Importantly, osteoclast-specific depletion of OPN or inhibition of osteoclastogenesis restored T cell function and enhanced ICB efficacy in preclinical cancer models, suggesting that targeting osteoclasts overcomes ICB resistance in patients with bone metastases. This study offers novel insights into the role of OPN, revealing its capacity to traverse from the skeletal microenvironment to distant sites, orchestrating widespread immunosuppression that extend well beyond the bone itself. As a pioneering investigation, it delineates the immunosuppression mechanism mediated by the osteoimmune axis and represents a significant advancement in the emerging field of osteoimmunology.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"10 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520595","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

The C-terminal Kinase Domain-Binding and Suppression Motif Prevents Constitutive Activation of FGFR2. c端激酶结构域结合和抑制基序阻止FGFR2的组成性激活。

IF 11.2 1区医学

Cancer research Pub Date : 2025-06-24 DOI: 10.1158/0008-5472.can-24-3349

Daniel Zingg,Chi-Chuan Lin,Julia Yemelyanenko,Lukasz Wieteska,Sjors M Kas,Onno B Bleijerveld,Xue Chao,Jinhyuk Bhin,Catrin Lutz,Ellen Wientjens,Sjoerd Klarenbeek,Giulia Zanetti,Stefano Annunziato,Bjørn Siteur,Eline van der Burg,Anne Paulien Drenth,Marieke van de Ven,Lodewyk F A Wessels,Maarten Altelaar,John E Ladbury,Jos Jonkers

{"title":"The C-terminal Kinase Domain-Binding and Suppression Motif Prevents Constitutive Activation of FGFR2.","authors":"Daniel Zingg,Chi-Chuan Lin,Julia Yemelyanenko,Lukasz Wieteska,Sjors M Kas,Onno B Bleijerveld,Xue Chao,Jinhyuk Bhin,Catrin Lutz,Ellen Wientjens,Sjoerd Klarenbeek,Giulia Zanetti,Stefano Annunziato,Bjørn Siteur,Eline van der Burg,Anne Paulien Drenth,Marieke van de Ven,Lodewyk F A Wessels,Maarten Altelaar,John E Ladbury,Jos Jonkers","doi":"10.1158/0008-5472.can-24-3349","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-3349","url":null,"abstract":"Genetic alterations in receptor tyrosine kinase (RTK) genes can generate potent oncogenic drivers. Truncation of the fibroblast growth factor receptor 2 (FGFR2) gene by its last exon 18 (E18) is caused by structural alterations, such as focal amplifications and gene fusions/rearrangements, as well as by mutations. All the E18-truncating FGFR2 variants (FGFR2ΔE18) act as strong driver alterations in cancer, and they commonly encode a receptor lacking the carboxy (C)-terminal tail. Here, we analyzed a compendium of Fgfr2-E18 variants to uncover the mechanism by which loss of the C-tail renders FGFR2 oncogenic. While permutation of previously annotated C-terminal FGFR motifs did not recapitulate the tumorigenicity of FGFR2ΔE18, the functional annotation efforts led to the discovery of a C-terminal phenylalanine-serine motif that mediates binding of the C-tail to the kinase domain and thereby suppresses FGFR2 kinase activity. Permutation of this kinase domain-binding and suppression (KDBS) motif in conjunction with other FGFR2-regulatory C-terminal sites fully phenocopied the oncogenic competence of FGFR2ΔE18. Together, these findings delineate how the C-terminal tail prevents FGFR2 from aberrant oncogenic activation.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"16 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478758","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

Tumor-Specific MHC-II Activates CD4+ and CD8+ T cells in Head and Neck Squamous Cell Carcinoma to Boost Immunotherapy Efficacy 肿瘤特异性MHC-II激活头颈部鳞状细胞癌的CD4+和CD8+ T细胞，提高免疫治疗效果

IF 11.2 1区医学

Cancer research Pub Date : 2025-06-20 DOI: 10.1158/0008-5472.can-24-4383

Yuying Zhang, Jinbang Li, Xiaoyu Guo, Zhao Gao, Junchen Pan, Sheng Nong, Jiyuan Ma, Gang Chen, Jiali Zhang

{"title":"Tumor-Specific MHC-II Activates CD4+ and CD8+ T cells in Head and Neck Squamous Cell Carcinoma to Boost Immunotherapy Efficacy","authors":"Yuying Zhang, Jinbang Li, Xiaoyu Guo, Zhao Gao, Junchen Pan, Sheng Nong, Jiyuan Ma, Gang Chen, Jiali Zhang","doi":"10.1158/0008-5472.can-24-4383","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-4383","url":null,"abstract":"Neoadjuvant immunotherapy is a first-line treatment for recurrent and metastatic head and neck squamous cell carcinoma. However, only a fraction of advanced HNSCC patients benefit from immunotherapy. Identifying accurate and accessible biomarkers is essential for optimal patient selection. Herein, we integrated single-cell RNA-sequencing and T cell receptor-sequencing to comprehensively characterize the tumor immune microenvironment (TIME) of HNSCC biopsies prior to a phase II neoadjuvant immunotherapy clinical trial. Tumor-specific MHC-II (tsMHC-II) was identified as a superior predictor of response to neoadjuvant immunotherapy in HNSCC compared to PD-L1. Mechanistically, tsMHC-II ignited a hot TIME and enhanced the effect of PD-1 blockade by recruiting T cells through the induction of chemokines, particularly CCL5. Moreover, tsMHC-II triggered a Th1 response and activated CD4+ and CD8+ T cell expansion, suppressing HNSCC growth in a CD4+ T-cell-dependent manner. Simultaneously, tsMHC-II facilitated an increase in PD-1+CD4+ T cells and a modest elevation in tumor PD-L1, thereby enhancing sensitivity to anti-PD-1 therapy. This study highlights that tsMHC-II, by generating an inflamed TIME, is crucial in enhancing the effectiveness of neoadjuvant immunotherapy in HNSCC.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"36 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335023","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