Cancer Cell最新文献_第7页

Many paths, one destination: Bridging the gap in cancer care 许多途径，一个目标：弥合癌症治疗的差距

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.026

Erik Sahai, Hongxia Wang, Marleen Kok, Catherine J. Wu, Lin Shen, John Carpten, César Serrano, Varun Venkataramani

引用次数: 0

New horizons at the interface of artificial intelligence and translational cancer research 人工智能与转化性癌症研究的新视野

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.018

Josephine Yates, Eliezer M. Van Allen

{"title":"New horizons at the interface of artificial intelligence and translational cancer research","authors":"Josephine Yates, Eliezer M. Van Allen","doi":"10.1016/j.ccell.2025.03.018","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.018","url":null,"abstract":"Artificial intelligence (AI) is increasingly being utilized in cancer research as a computational strategy for analyzing multiomics datasets. Advances in single-cell and spatial profiling technologies have contributed significantly to our understanding of tumor biology, and AI methodologies are now being applied to accelerate translational efforts, including target discovery, biomarker identification, patient stratification, and therapeutic response prediction. Despite these advancements, the integration of AI into clinical workflows remains limited, presenting both challenges and opportunities. This review discusses AI applications in multiomics analysis and translational oncology, emphasizing their role in advancing biological discoveries and informing clinical decision-making. Key areas of focus include cellular heterogeneity, tumor microenvironment interactions, and AI-aided diagnostics. Challenges such as reproducibility, interpretability of AI models, and clinical integration are explored, with attention to strategies for addressing these hurdles. Together, these developments underscore the potential of AI and multiomics to enhance precision oncology and contribute to advancements in cancer care.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"25 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827141","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

Bridging the gap: The future of cancer research and clinical oncology in Cancer Cell 弥合差距：癌症研究和临床肿瘤学的未来

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.024

Steve Mao

引用次数: 0

CAR-T therapy in solid tumors CAR-T疗法在实体瘤中的应用

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.019

Bing Du, Juliang Qin, Boxu Lin, Jiqin Zhang, Dali Li, Mingyao Liu

引用次数: 0

Pan-cancer human brain metastases atlas at single-cell resolution 单细胞分辨率的泛癌人脑转移图谱

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.025

Xudong Xing, Jian Zhong, Jana Biermann, Hao Duan, Xinyu Zhang, Yu Shi, Yixin Gao, Kejun He, Duanyang Zhai, Feng Luo, Yanxing Lai, Feizhe Xiao, Wenying Wang, Mengru Wang, Jianguo Xu, Hao Liu, Jiaze Tang, Liangzhao Chu, Tunan Chen, Edridge K. D’Souza, Fan Bai

{"title":"Pan-cancer human brain metastases atlas at single-cell resolution","authors":"Xudong Xing, Jian Zhong, Jana Biermann, Hao Duan, Xinyu Zhang, Yu Shi, Yixin Gao, Kejun He, Duanyang Zhai, Feng Luo, Yanxing Lai, Feizhe Xiao, Wenying Wang, Mengru Wang, Jianguo Xu, Hao Liu, Jiaze Tang, Liangzhao Chu, Tunan Chen, Edridge K. D’Souza, Fan Bai","doi":"10.1016/j.ccell.2025.03.025","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.025","url":null,"abstract":"Brain metastases (BrMs) remain a major clinical and therapeutic challenge in patients with metastatic cancers. However, advances in our understanding of BrM have been hampered by the constrained sample size and resolution of BrM profiling studies. Here, we perform integrative single-cell RNA sequencing analysis on 108 BrM samples and 111 primary tumor (PTs) samples to investigate the characteristics and remodeling of cell states and composition across cancer lineages and subsets. Recurring and enriched features of malignant cells are increased chromosomal instability, marked proliferative and angiogenic hallmarks, and adoption of a neural-like BrM-associated metaprogram. Immunosuppressive myeloid and stromal subsets dominate the BrM tumor microenvironment, which are associated with poor prognosis and resistance to immunotherapy. Furthermore, five distinct BrM ecotypes are identified, correlating with specific histopathological patterns and clinical characteristics. This work defines hallmarks of BrM biology across cancer types and suggests that shared dependencies may exist, which may be exploited clinically.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"89 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814006","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

Radiotherapy promotes cuproptosis and synergizes with cuproptosis inducers to overcome tumor radioresistance 放疗促进铜体增生，并与铜体增生诱导剂协同克服肿瘤放射耐药

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.031

Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Boyi Gan

{"title":"Radiotherapy promotes cuproptosis and synergizes with cuproptosis inducers to overcome tumor radioresistance","authors":"Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Boyi Gan","doi":"10.1016/j.ccell.2025.03.031","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.031","url":null,"abstract":"Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins—both hallmarks of cuproptosis—in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the expression of copper-sequestering metallothionein (MT) 1E/X, thereby mitigating cuproptosis and contributing to radioresistance. Copper ionophore treatment sensitizes radioresistant cancer cells and cell line- and patient-derived xenografts to RT by potentiating cuproptosis. Our findings unveil a link between RT and cuproptosis and inform a therapeutic strategy to overcome tumor radioresistance by targeting cuproptosis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"107 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814001","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

Spatial determinants of antibody-drug conjugate SHR-A1811 efficacy in neoadjuvant treatment for HER2-positive breast cancer SHR-A1811抗体-药物偶联物在her2阳性乳腺癌新辅助治疗中疗效的空间决定因素

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.017

Ding Ma, Lei-Jie Dai, Xiang-Rong Wu, Cheng-Lin Liu, Shen Zhao, Hang Zhang, Li Chen, Yi Xiao, Ming Li, Yi-Zhi Zhao, Lin Yang, Tong Zhou, Jun-Jie Li, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao

{"title":"Spatial determinants of antibody-drug conjugate SHR-A1811 efficacy in neoadjuvant treatment for HER2-positive breast cancer","authors":"Ding Ma, Lei-Jie Dai, Xiang-Rong Wu, Cheng-Lin Liu, Shen Zhao, Hang Zhang, Li Chen, Yi Xiao, Ming Li, Yi-Zhi Zhao, Lin Yang, Tong Zhou, Jun-Jie Li, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao","doi":"10.1016/j.ccell.2025.03.017","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.017","url":null,"abstract":"Selecting optimal candidates for next-generation anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) remains challenging. We conduct a prespecified translational study to identify treatment biomarkers in SHR-A1811-treated HER2-positive breast cancer patients from the phase 2 neoadjuvant FASCINATE-N trial using DNA and RNA sequencing, computational pathology, and single-cell in situ spatial imaging. In the hormone receptor (HR)-negative subgroup, a higher proportion and more infiltration of immune cells (i.e., tumor-infiltrating lymphocytes [TILs]), particularly cytotoxic T cells, are associated with better treatment responses. In the HR-positive subgroup, the closeness and aggregation of HER2-strong-positive tumor cells, as opposed to a uniform distribution, are linked to a lower response rate and HER2 luminal-like (HER2-LUM) subtype, which more closely resembles HR+/HER2− breast cancer. In addition, we develop a clinically practical predictive model capable of predicting neoadjuvant treatment responses to SHR-A1811 and other novel ADCs based on clinicopathological characteristics and pathological images.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"3 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814002","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

Neoadjuvant toripalimab plus nimotuzumab combined with taxol-based chemotherapy in locally advanced penile squamous cell carcinoma 局部晚期阴茎鳞状细胞癌的新辅助托利帕利单抗加尼莫妥珠单抗联合紫杉醇化疗

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.023

Xin An, Sheng Jie Guo, Ru Yan, Ting Xue, Long Bin Xiong, Hua Li Ma, Cong Xue, Ying Chun Zhang, Ji Bin Li, Mei Ting Chen, Zai Shang Li, Ting Yu Liu, Zhi Ling Zhang, Pei Dong, Yong Hong Li, Kai Yao, Zhi Quan Hu, Xiao Feng Chen, Jie Xin Luo, Yong Hong Lei, Hui Han

{"title":"Neoadjuvant toripalimab plus nimotuzumab combined with taxol-based chemotherapy in locally advanced penile squamous cell carcinoma","authors":"Xin An, Sheng Jie Guo, Ru Yan, Ting Xue, Long Bin Xiong, Hua Li Ma, Cong Xue, Ying Chun Zhang, Ji Bin Li, Mei Ting Chen, Zai Shang Li, Ting Yu Liu, Zhi Ling Zhang, Pei Dong, Yong Hong Li, Kai Yao, Zhi Quan Hu, Xiao Feng Chen, Jie Xin Luo, Yong Hong Lei, Hui Han","doi":"10.1016/j.ccell.2025.03.023","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.023","url":null,"abstract":"The conventional neoadjuvant chemotherapy regimen for locally advanced penile squamous cell carcinoma (La-PSCC) has shown moderate response rates and survival benefits. This single-arm, phase II trial (NCT04475016<svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>) evaluated a neoadjuvant regimen of four cycles of toripalimab (anti-PD-1 antibody), nimotuzumab (anti-EGFR antibody), and taxol-based chemotherapy (TNT), followed by consolidative surgery. The primary endpoint was the pathological complete response (pCR) rate. Among 29 enrolled patients, 24 (82.8%) underwent consolidative surgery, with 14 (48.3%, 95% confidence interval [CI], 29.4–67.5%) achieving pCR. The objective response rate (ORR) was 82.8% (95% CI, 64.2–94.2). Median follow-up was 39.97 months, with two-year overall survival (OS) and progression-free survival (PFS) rates of 72.4% and 65.5%. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 12 (41.4%) patients, with no treatment-related deaths. Biomarker analysis identified PD-L1 expression, TP53 mutation status, and CD8+ T cell density as potential predictive markers. Therefore, neoadjuvant TNT shows promising anti-tumor activity and acceptable toxicity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"60 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814004","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

ZEB2 is a master switch controlling the tumor-associated macrophage program ZEB2是控制肿瘤相关巨噬细胞程序的主开关

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.021

Fadi Sheban, Truong San Phan, Ken Xie, Florian Ingelfinger, Chamutal Gur, Yuval Shapir Itai, Ronnie Blecher-Gonen, Chunsong Yu, Roberto Avellino, Paulina Chalan, Kiara Freitag, Ido Yofe, Vladimir Yutkin, Pierre Boyeau, Can Ergen, Justin Hong, Kfir Mazuz, Yuxiao Liu, Kangming Chen, Rony Dahan, Ido Amit

{"title":"ZEB2 is a master switch controlling the tumor-associated macrophage program","authors":"Fadi Sheban, Truong San Phan, Ken Xie, Florian Ingelfinger, Chamutal Gur, Yuval Shapir Itai, Ronnie Blecher-Gonen, Chunsong Yu, Roberto Avellino, Paulina Chalan, Kiara Freitag, Ido Yofe, Vladimir Yutkin, Pierre Boyeau, Can Ergen, Justin Hong, Kfir Mazuz, Yuxiao Liu, Kangming Chen, Rony Dahan, Ido Amit","doi":"10.1016/j.ccell.2025.03.021","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.021","url":null,"abstract":"Tumor-associated macrophages (TAMs) are key mediators of tumor immune evasion. However, their regulatory circuits and checkpoints are partially understood. Here, we generated a TAM regulatory network by integrating human tumors single-cell RNA sequencing (scRNA-seq) data with a dedicated CRISPR screen. Using a deep generative model, we constructed a gene perturbation network linking individual candidates with prototypical TAM functions. We identified Zeb2 as the master regulator of TAM programs, orchestrating suppression of type-I interferon response and antigen presentation alongside activation of immune suppression programs. Genetic ablation of ZEB2 reprograms TAM function and identity on the chromatin, RNA, and protein levels. In macrophage-rich human tumors, ZEB2 expression is associated with poor prognosis. Selective Zeb2 in vivo targeting reprograms TAMs and mobilizes systemic T cell responses, achieving robust tumor clearance. Overall, our study generates a detailed roadmap of TAM gene circuits and identifies ZEB2 as a master switch with therapeutic potential.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"183 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814007","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

AI-driven biomarkers for antibody-drug conjugates 人工智能驱动的抗体-药物偶联物生物标志物

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-10 DOI: 10.1016/j.ccell.2025.03.020

Sherene Loi, Roberto Salgado

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