Cancer Cell最新文献_第8页

Th9 Cells Represent a Unique Subset of CD4+ T Cells Endowed with the Ability to Eradicate Advanced Tumors Th9 细胞代表了一种独特的 CD4+ T 细胞亚群，具有消灭晚期肿瘤的能力

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-07-08 DOI: 10.1016/j.ccell.2024.06.008

Yong Lu, Qiang Wang, Gang Xue, Enguang Bi, Xingzhe Ma, Aibo Wang, Jianfei Qian, Chen Dong, Qing Yi

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HRS-4642: The next piece of the puzzle to keep KRAS in check HRS-4642：控制 KRAS 的下一块拼图

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-07-08 DOI: 10.1016/j.ccell.2024.06.005

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Multi-scale signaling and tumor evolution in high-grade gliomas 高级别胶质瘤的多尺度信号传导与肿瘤演化

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-07-08 DOI: 10.1016/j.ccell.2024.06.004

Jingxian Liu, Song Cao, Kathleen J. Imbach, Marina A. Gritsenko, Tung-Shing M. Lih, Jennifer E. Kyle, Tomer M. Yaron-Barir, Zev A. Binder, Yize Li, Ilya Strunilin, Yi-Ting Wang, Chia-Feng Tsai, Weiping Ma, Lijun Chen, Natalie M. Clark, Andrew Shinkle, Nataly Naser Al Deen, Wagma Caravan, Andrew Houston, Faria Anjum Simin, Li Ding

{"title":"Multi-scale signaling and tumor evolution in high-grade gliomas","authors":"Jingxian Liu, Song Cao, Kathleen J. Imbach, Marina A. Gritsenko, Tung-Shing M. Lih, Jennifer E. Kyle, Tomer M. Yaron-Barir, Zev A. Binder, Yize Li, Ilya Strunilin, Yi-Ting Wang, Chia-Feng Tsai, Weiping Ma, Lijun Chen, Natalie M. Clark, Andrew Shinkle, Nataly Naser Al Deen, Wagma Caravan, Andrew Houston, Faria Anjum Simin, Li Ding","doi":"10.1016/j.ccell.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.004","url":null,"abstract":"Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561729","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

Medulloblastoma subgrouping at first sight 髓母细胞瘤亚组初探

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-07-08 DOI: 10.1016/j.ccell.2024.06.011

Marc Remke, Vijay Ramaswamy

引用次数: 0

Advancing presurgical non-invasive molecular subgroup prediction in medulloblastoma using artificial intelligence and MRI signatures 利用人工智能和磁共振成像特征推进髓母细胞瘤术前非侵入性分子亚组预测

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-06-27 DOI: 10.1016/j.ccell.2024.06.002

Yan-Ran (Joyce) Wang, Pengcheng Wang, Zihan Yan, Quan Zhou, Fatma Gunturkun, Peng Li, Yanshen Hu, Wei Emma Wu, Kankan Zhao, Michael Zhang, Haoyi Lv, Lehao Fu, Jiajie Jin, Qing Du, Haoyu Wang, Kun Chen, Liangqiong Qu, Keldon Lin, Michael Iv, Hao Wang, Jian Gong

{"title":"Advancing presurgical non-invasive molecular subgroup prediction in medulloblastoma using artificial intelligence and MRI signatures","authors":"Yan-Ran (Joyce) Wang, Pengcheng Wang, Zihan Yan, Quan Zhou, Fatma Gunturkun, Peng Li, Yanshen Hu, Wei Emma Wu, Kankan Zhao, Michael Zhang, Haoyi Lv, Lehao Fu, Jiajie Jin, Qing Du, Haoyu Wang, Kun Chen, Liangqiong Qu, Keldon Lin, Michael Iv, Hao Wang, Jian Gong","doi":"10.1016/j.ccell.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.002","url":null,"abstract":"Global investigation of medulloblastoma has been hindered by the widespread inaccessibility of molecular subgroup testing and paucity of data. To bridge this gap, we established an international molecularly characterized database encompassing 934 medulloblastoma patients from thirteen centers across China and the United States. We demonstrate how image-based machine learning strategies have the potential to create an alternative pathway for non-invasive, presurgical, and low-cost molecular subgroup prediction in the clinical management of medulloblastoma. Our robust validation strategies—including cross-validation, external validation, and consecutive validation—demonstrate the model’s efficacy as a generalizable molecular diagnosis classifier. The detailed analysis of MRI characteristics replenishes the understanding of medulloblastoma through a nuanced radiographic lens. Additionally, comparisons between East Asia and North America subsets highlight critical management implications. We made this comprehensive dataset, which includes MRI signatures, clinicopathological features, treatment variables, and survival data, publicly available to advance global medulloblastoma research.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462085","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}

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Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer HRS-4642 的抗肿瘤疗效及其与蛋白酶体抑制剂联合治疗 KRAS G12D 突变癌症的潜力

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-06-27 DOI: 10.1016/j.ccell.2024.06.001

Caicun Zhou, Chongyang Li, Libo Luo, Xin Li, Keyi Jia, Ning He, Shiqi Mao, Wanying Wang, Chuchu Shao, Xinyu Liu, Kan Huang, Yaxin Yu, Xinlei Cai, Yingxue Chen, Zican Dai, Wei Li, Jia Yu, Jiayu Li, Feng Shen, Zaiyong Wang, Shengxiang Ren

{"title":"Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer","authors":"Caicun Zhou, Chongyang Li, Libo Luo, Xin Li, Keyi Jia, Ning He, Shiqi Mao, Wanying Wang, Chuchu Shao, Xinyu Liu, Kan Huang, Yaxin Yu, Xinlei Cai, Yingxue Chen, Zican Dai, Wei Li, Jia Yu, Jiayu Li, Feng Shen, Zaiyong Wang, Shengxiang Ren","doi":"10.1016/j.ccell.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.001","url":null,"abstract":"KRAS G12D is the most frequently mutated oncogenic KRAS subtype in solid tumors and remains undruggable in clinical settings. Here, we developed a high affinity, selective, long-acting, and non-covalent KRAS G12D inhibitor, HRS-4642, with an affinity constant of 0.083 nM. HRS-4642 demonstrated robust efficacy against KRAS G12D-mutant cancers both in vitro and in vivo. Importantly, in a phase 1 clinical trial, HRS-4642 exhibited promising anti-tumor activity in the escalating dosing cohorts. Furthermore, the sensitization and resistance spectrum for HRS-4642 was deciphered through genome-wide CRISPR-Cas9 screening, which unveiled proteasome as a sensitization target. We further observed that the proteasome inhibitor, carfilzomib, improved the anti-tumor efficacy of HRS-4642. Additionally, HRS-4642, either as a single agent or in combination with carfilzomib, reshaped the tumor microenvironment toward an immune-permissive one. In summary, this study provides potential therapies for patients with KRAS G12D-mutant cancers, for whom effective treatments are currently lacking.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462115","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}

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Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors 免疫疗法介导的实体瘤消除需要瘤内免疫三联体

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-06-20 DOI: 10.1016/j.ccell.2024.05.025

Gabriel Espinosa-Carrasco, Edison Chiu, Aurora Scrivo, Paul Zumbo, Asim Dave, Doron Betel, Sung Wook Kang, Hee-Jin Jang, Matthew D. Hellmann, Bryan M. Burt, Hyun-Sung Lee, Andrea Schietinger

{"title":"Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors","authors":"Gabriel Espinosa-Carrasco, Edison Chiu, Aurora Scrivo, Paul Zumbo, Asim Dave, Doron Betel, Sung Wook Kang, Hee-Jin Jang, Matthew D. Hellmann, Bryan M. Burt, Hyun-Sung Lee, Andrea Schietinger","doi":"10.1016/j.ccell.2024.05.025","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.05.025","url":null,"abstract":"Tumor-specific CD8+ T cells are frequently dysfunctional and unable to halt tumor growth. We investigated whether tumor-specific CD4+ T cells can be enlisted to overcome CD8+ T cell dysfunction within tumors. We find that the spatial positioning and interactions of CD8+ and CD4+ T cells, but not their numbers, dictate anti-tumor responses in the context of adoptive T cell therapy as well as immune checkpoint blockade (ICB): CD4+ T cells must engage with CD8+ T cells on the same dendritic cell during the effector phase, forming a three-cell-type cluster (triad) to license CD8+ T cell cytotoxicity and cancer cell elimination. When intratumoral triad formation is disrupted, tumors progress despite equal numbers of tumor-specific CD8+ and CD4+ T cells. In patients with pleural mesothelioma treated with ICB, triads are associated with clinical responses. Thus, CD4+ T cells and triads are required for CD8+ T cell cytotoxicity during the effector phase and tumor elimination.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430733","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}

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IRF4 requires ARID1A to establish plasma cell identity in multiple myeloma IRF4需要ARID1A才能在多发性骨髓瘤中建立浆细胞特性

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-06-20 DOI: 10.1016/j.ccell.2024.05.026

Arnold Bolomsky, Michele Ceribelli, Sebastian Scheich, Kristina Rinaldi, Da Wei Huang, Papiya Chakraborty, Lisette Pham, George W. Wright, Tony Hsiao, Vivian Morris, Jaewoo Choi, James D. Phelan, Ronald J. Holewinski, Thorkell Andresson, Jan Wisniewski, Deanna Riley, Stefania Pittaluga, Elizabeth Hill, Craig J. Thomas, Jagan Muppidi, Ryan M. Young

{"title":"IRF4 requires ARID1A to establish plasma cell identity in multiple myeloma","authors":"Arnold Bolomsky, Michele Ceribelli, Sebastian Scheich, Kristina Rinaldi, Da Wei Huang, Papiya Chakraborty, Lisette Pham, George W. Wright, Tony Hsiao, Vivian Morris, Jaewoo Choi, James D. Phelan, Ronald J. Holewinski, Thorkell Andresson, Jan Wisniewski, Deanna Riley, Stefania Pittaluga, Elizabeth Hill, Craig J. Thomas, Jagan Muppidi, Ryan M. Young","doi":"10.1016/j.ccell.2024.05.026","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.05.026","url":null,"abstract":"Multiple myeloma (MM) is an incurable plasma cell malignancy that exploits transcriptional networks driven by IRF4. We employ a multi-omics approach to discover IRF4 vulnerabilities, integrating functional genomics screening, spatial proteomics, and global chromatin mapping. ARID1A, a member of the SWI/SNF chromatin remodeling complex, is required for IRF4 expression and functionally associates with IRF4 protein on chromatin. Deleting Arid1a in activated murine B cells disrupts IRF4-dependent transcriptional networks and blocks plasma cell differentiation. Targeting SWI/SNF activity leads to rapid loss of IRF4-target gene expression and quenches global amplification of oncogenic gene expression by MYC, resulting in profound toxicity to MM cells. Notably, MM patients with aggressive disease bear the signature of SWI/SNF activity, and SMARCA2/4 inhibitors remain effective in immunomodulatory drug (IMiD)-resistant MM cells. Moreover, combinations of SWI/SNF and MEK inhibitors demonstrate synergistic toxicity to MM cells, providing a promising strategy for relapsed/refractory disease.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435864","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}

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How can we integrate the biology of breast cancer cell dormancy into clinical practice? 如何将乳腺癌细胞休眠的生物学原理融入临床实践？

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-06-20 DOI: 10.1016/j.ccell.2024.05.023

Islam E. Elkholi, April A.N. Rose, Julio A. Aguirre-Ghiso, Jean-François Côté

引用次数: 0

Neoadjuvant SHR-1701 with or without chemotherapy in unresectable stage III non-small-cell lung cancer: A proof-of-concept, phase 2 trial 不可切除的 III 期非小细胞肺癌的新辅助 SHR-1701 化疗或不化疗：概念验证2期试验

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-06-20 DOI: 10.1016/j.ccell.2024.05.024

Qing Zhou, Yi Pan, Xuening Yang, Yanqiu Zhao, Guang Han, Qingsong Pang, Zhenfa Zhang, Qifeng Wang, Jun Yao, Hui Wang, Weihua Yang, Baogang Liu, Qixun Chen, Xianghui Du, Kaican Cai, Baosheng Li, Yunchao Huang, Xiao Li, Li Song, Wei Shi, Yi-Long Wu

{"title":"Neoadjuvant SHR-1701 with or without chemotherapy in unresectable stage III non-small-cell lung cancer: A proof-of-concept, phase 2 trial","authors":"Qing Zhou, Yi Pan, Xuening Yang, Yanqiu Zhao, Guang Han, Qingsong Pang, Zhenfa Zhang, Qifeng Wang, Jun Yao, Hui Wang, Weihua Yang, Baogang Liu, Qixun Chen, Xianghui Du, Kaican Cai, Baosheng Li, Yunchao Huang, Xiao Li, Li Song, Wei Shi, Yi-Long Wu","doi":"10.1016/j.ccell.2024.05.024","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.05.024","url":null,"abstract":"We conducted a proof-of-concept, phase 2 trial to assess neoadjuvant SHR-1701 with or without chemotherapy, followed by surgery or radiotherapy, and then consolidation SHR-1701 in unresectable stage III non-small-cell lung cancer (NSCLC). In the primary cohort of patients receiving neoadjuvant combination therapy (n = 97), both primary endpoints were met, with a post-induction objective response rate of 58% (95% confidence interval [CI] 47–68) and an 18-month event-free survival (EFS) rate of 56.6% (95% CI 45.2–66.5). Overall, 27 (25%) patients underwent surgery; all achieved R0 resection. Among them, 12 (44%) major pathological responses and seven (26%) pathological complete responses were recorded. The 18-month EFS rate was 74.1% (95% CI 53.2–86.7) in surgical patients and 57.3% (43.0–69.3) in radiotherapy-treated patients. Neoadjuvant SHR-1701 with chemotherapy, followed by surgery or radiotherapy, showed promising efficacy with a tolerable safety profile in unresectable stage III NSCLC. Surgical conversion was feasible in a notable proportion of patients and associated with better survival outcomes.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430713","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