Cancer discovery最新文献_第2页

A Roadmap to Precision Immunotherapy for Early-Stage Non-Small Cell Lung Cancer. 早期非小细胞肺癌精确免疫治疗路线图

IF 29.7 1区医学

Cancer discovery Pub Date : 2025-05-02 DOI: 10.1158/2159-8290.CD-25-0262

Alessandra Vaccaro, Zahraa Rahal, Humam Kadara, Tina Cascone

引用次数: 0

Presence of Tertiary Lymphoid Structures and Exhausted Tissue-Resident T Cells Determines Clinical Response to PD-1 Blockade in Renal Cell Carcinoma. 三级淋巴样结构和耗竭的组织驻留T细胞的存在决定了肾细胞癌对PD-1阻断的临床反应。

IF 29.7 1区医学

Cancer discovery Pub Date : 2025-05-02 DOI: 10.1158/2159-8290.CD-24-0991

Miya B Hugaboom, Lena V Wirth, Kelly Street, Neil Ruthen, Opeyemi A Jegede, Nicholas R Schindler, Valisha Shah, Jacob P Zaemes, Nourhan El Ahmar, Sayed Matar, Varunika Savla, Toni K Choueiri, Thomas Denize, Destiny J West, David F McDermott, Elizabeth R Plimack, Jeffrey A Sosman, Naomi B Haas, Mark N Stein, Robert Alter, Mehmet A Bilen, Michael E Hurwitz, Hans Hammers, Sabina Signoretti, Michael B Atkins, Catherine J Wu, David A Braun

引用次数: 0

Under (Genetic Selection) Pressure: Human Tumors and Human Populations in Hypoxia. 在（遗传选择）压力下：人类肿瘤和缺氧环境下的人类种群。

IF 28.2 1区医学

Cancer discovery Pub Date : 2025-04-30 DOI: 10.1158/2159-8290.cd-25-0175

Frank S Lee

引用次数: 0

FABP4-tastic Pancreatic Stellate Cells Coddle KITL to Uphold Inherent Microenvironmental Tumor Suppression. FABP4-tastic胰腺星状细胞对KITL进行加热以维持固有的微环境肿瘤抑制。

IF 28.2 1区医学

Cancer discovery Pub Date : 2025-04-30 DOI: 10.1158/2159-8290.cd-25-0212

Aleksandr Dolskii,Edna Cukierman

引用次数: 0

Cancer-Associated Cachexia: Bridging Clinical Findings with Mechanistic Insights in Human Studies. 癌症相关恶病质：连接临床发现与人体研究的机制见解。

IF 28.2 1区医学

Cancer discovery Pub Date : 2025-04-29 DOI: 10.1158/2159-8290.cd-25-0293

Kexin Koh,Rachel Scott,Elizabeth M Cespedes Feliciano,Tobias Janowitz,Marcus D Goncalves,Eileen P White,Barry J A Laird,Kerstin Haase,Mariam Jamal-Hanjani

引用次数: 0

Evolving CAR T-Cell Therapy to Overcome the Barriers in Treating Pediatric Central Nervous System Tumors 不断发展的CAR - t细胞疗法克服治疗小儿中枢神经系统肿瘤的障碍

IF 28.2 1区医学

Cancer discovery Pub Date : 2025-04-29 DOI: 10.1158/2159-8290.cd-24-1465

Andrea Timpanaro, Edward Z. Song, Nour Amwas, Chu-Hsuan Chiu, Rebecca Ronsley, Mallory R. Taylor, Jessica B. Foster, Leo D. Wang, Nicholas A. Vitanza

{"title":"Evolving CAR T-Cell Therapy to Overcome the Barriers in Treating Pediatric Central Nervous System Tumors","authors":"Andrea Timpanaro, Edward Z. Song, Nour Amwas, Chu-Hsuan Chiu, Rebecca Ronsley, Mallory R. Taylor, Jessica B. Foster, Leo D. Wang, Nicholas A. Vitanza","doi":"10.1158/2159-8290.cd-24-1465","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1465","url":null,"abstract":"Central nervous system (CNS) tumors are a leading cause of pediatric cancer-related death. Chimeric antigen receptor (CAR) T cells are an innovative approach for these affected children who are in desperate need of novel therapies, but CNS-directed cellular therapies have only recently advanced to the clinic. Although early-phase trials have begun to demonstrate the feasibility of manufacturing fractionated doses and the tolerability of repeated infusions for children with CNS tumors, major challenges remain. In this review, we will take an inventory of the current state of the pediatric CNS CAR T-cell field through the lens of translational obstacles to broader clinical success. Significance: CNS tumors are the leading cause of cancer-related death in children, highlighting the dire need for new treatment strategies. CAR T cells represent a unique approach, distinct from the cytotoxic chemotherapies and small-molecule inhibitors that have dominated the clinical trial space for decades. Phase I CAR T-cell trials have shown feasibility and possible efficacy against pediatric CNS tumors; however, many challenges must be overcome if these therapeutics are going to be beneficial to most affected children. Although rapid translational development and early-phase trials have quickly evolved our understanding, the pediatric CNS CAR T-cell community now yearns for critical assessments and open dialogue about overcoming the remaining obstacles ahead.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"86 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889585","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

A RAS(ON) multi-selective inhibitor combination therapy triggers long-term tumor control through senescence-associated tumor-immune equilibrium in PDAC RAS（ON）多选择性抑制剂联合治疗通过PDAC中衰老相关的肿瘤免疫平衡触发长期肿瘤控制

IF 28.2 1区医学

Cancer discovery Pub Date : 2025-04-29 DOI: 10.1158/2159-8290.cd-24-1425

Caroline Broderick, Riccardo Mezzadra, Exequiel M. Sisso, Felix Mbuga, Rashi Raghulan, Almudena Chaves Perez, Amanda Kulick, Lingyan Jiang, Jingjing Jiang, Yu-Jui Ho, Janelle Simon, Eric Rosiek, Eric Chan, Aveline Filliol, Ronan Chaligne, Elisa de Stanchina, Ximo Pechuan-Jorge, Andrea Schietinger, Mallika Singh, Scott W. Lowe

{"title":"A RAS(ON) multi-selective inhibitor combination therapy triggers long-term tumor control through senescence-associated tumor-immune equilibrium in PDAC","authors":"Caroline Broderick, Riccardo Mezzadra, Exequiel M. Sisso, Felix Mbuga, Rashi Raghulan, Almudena Chaves Perez, Amanda Kulick, Lingyan Jiang, Jingjing Jiang, Yu-Jui Ho, Janelle Simon, Eric Rosiek, Eric Chan, Aveline Filliol, Ronan Chaligne, Elisa de Stanchina, Ximo Pechuan-Jorge, Andrea Schietinger, Mallika Singh, Scott W. Lowe","doi":"10.1158/2159-8290.cd-24-1425","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1425","url":null,"abstract":"Pharmacological inhibition of oncogenic RAS represents an attractive strategy to target pancreatic ductal adenocarcinoma (PDAC), an almost ubiquitously RAS-driven disease. However, initial responses to targeted monotherapy inhibition of active RAS can be followed by relapses, potentially driven by the persistence of drug-tolerant tumor cells. To target these ‘persister’ cells, we investigated strategies to increase their immune visibility in mouse models of PDAC. We show that combining a RAS(ON) multi-selective inhibitor with the CDK4/6 inhibitor palbociclib drives persister cells into a senescent-like state, which coincides with improved tumor control and substantial remodeling of the tumor microenvironment. Combining RAS(ON) and CDK4/6 inhibition with a CD40 agonist results in durable regressions and CD4 T cell-dependent tumor-immune equilibrium. Our studies reveal a combinatorial approach that circumvents resistance to RAS(ON) inhibitor monotherapy in preclinical models and demonstrate a mechanism by which therapy-induced senescence can be reinforced by the immune system, resulting in durable tumor control.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"34 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889584","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

Integrating ctDNA Analysis and Radiomics for Dynamic Risk Assessment in Localized Lung Cancer 整合ctDNA分析和放射组学用于局部肺癌的动态风险评估

IF 28.2 1区医学

Cancer discovery Pub Date : 2025-04-29 DOI: 10.1158/2159-8290.cd-24-1704

Everett J. Moding, Mohammad Shahrokh Esfahani, Cheng Jin, Angela B. Hui, Barzin Y. Nabet, Yufei Liu, Jacob J. Chabon, Michael S. Binkley, David M. Kurtz, Emily G. Hamilton, Aadel A. Chaudhuri, Chih Long Liu, Zhe Li, Rene F. Bonilla, Alice L. Jiang, Brianna C. Lau, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Luyang Yao, Saumil Gandhi, Zhongxing Liao, Millie Das, Kavitha J. Ramchandran, Sukhmani K. Padda, Joel W. Neal, Heather A. Wakelee, Michael F. Gensheimer, Billy W. Loo, Ruijiang Li, Steven H. Lin, Ash A. Alizadeh, Maximilian Diehn

{"title":"Integrating ctDNA Analysis and Radiomics for Dynamic Risk Assessment in Localized Lung Cancer","authors":"Everett J. Moding, Mohammad Shahrokh Esfahani, Cheng Jin, Angela B. Hui, Barzin Y. Nabet, Yufei Liu, Jacob J. Chabon, Michael S. Binkley, David M. Kurtz, Emily G. Hamilton, Aadel A. Chaudhuri, Chih Long Liu, Zhe Li, Rene F. Bonilla, Alice L. Jiang, Brianna C. Lau, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Luyang Yao, Saumil Gandhi, Zhongxing Liao, Millie Das, Kavitha J. Ramchandran, Sukhmani K. Padda, Joel W. Neal, Heather A. Wakelee, Michael F. Gensheimer, Billy W. Loo, Ruijiang Li, Steven H. Lin, Ash A. Alizadeh, Maximilian Diehn","doi":"10.1158/2159-8290.cd-24-1704","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-24-1704","url":null,"abstract":"The complementarity and clinical utility of combining liquid biopsies and radiomic image analysis has not been demonstrated. ctDNA minimal residual disease after chemoradiotherapy (CRT) for non–small cell lung cancer (NSCLC) is highly prognostic, but on-treatment biomarkers are needed to enable response-adapted therapies. In this study, we analyzed 418 patients with NSCLC undergoing CRT to develop and validate a novel dynamic risk model that accurately predicts ultimate progression-free survival during treatment. We optimize tissue-free variant calling from plasma samples to facilitate ctDNA monitoring and demonstrate the importance of accounting for persistent clonal hematopoiesis variants. We show that mid-CRT ctDNA concentration is prognostic for disease progression and integrate additional pre-CRT risk factors, including radiomics, into a combined model that improves outcome prediction. Our results suggest that tumor features, radiomics, and mid-CRT ctDNA analysis are complementary and can identify patients at high and low risk of progression to potentially enable response-adapted therapies. Significance: This study demonstrates that combining tumor features, radiomics, and ctDNA analysis improves outcome prediction in NSCLC treated with CRT therapy. Our integrated model could enable personalized and response-adapted therapies to reduce toxicity and improve outcomes in patients.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"43 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889586","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

Detection of brain cancer using genome-wide cell-free DNA fragmentomes. 利用全基因组无细胞DNA片段组检测脑癌。

IF 28.2 1区医学

Cancer discovery Pub Date : 2025-04-29 DOI: 10.1158/2159-8290.cd-25-0074

Dimitrios Mathios,Noushin Niknafs,Akshaya V Annapragada,Ernest J Bobeff,Elaine J Chiao,Kavya Boyapati,Keerti Boyapati,Sarah Short,Adrianna L Bartolomucci,Stephen Cristiano,Shashikant Koul,Nicholas A Vulpescu,Leonardo Ferreira,Jamie E Medina,Daniel C Bruhm,Vilmos Adleff,Małgorzata Podstawka,Patrycja Stanisławska,Chul-Kee Park,Judy Huang,Gary L Gallia,Henry Brem,Debraj Mukherjee,Justin M Caplan,Jon Weingart,Christopher M Jackson,Michael Lim,Jillian Phallen,Robert B Scharpf,Victor E Velculescu

{"title":"Detection of brain cancer using genome-wide cell-free DNA fragmentomes.","authors":"Dimitrios Mathios,Noushin Niknafs,Akshaya V Annapragada,Ernest J Bobeff,Elaine J Chiao,Kavya Boyapati,Keerti Boyapati,Sarah Short,Adrianna L Bartolomucci,Stephen Cristiano,Shashikant Koul,Nicholas A Vulpescu,Leonardo Ferreira,Jamie E Medina,Daniel C Bruhm,Vilmos Adleff,Małgorzata Podstawka,Patrycja Stanisławska,Chul-Kee Park,Judy Huang,Gary L Gallia,Henry Brem,Debraj Mukherjee,Justin M Caplan,Jon Weingart,Christopher M Jackson,Michael Lim,Jillian Phallen,Robert B Scharpf,Victor E Velculescu","doi":"10.1158/2159-8290.cd-25-0074","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0074","url":null,"abstract":"Diagnostic delays in patients with brain cancer are common and can impact patient outcome. Development of a blood-based assay for detection of brain cancers could accelerate brain cancer diagnosis. In this study, we analyzed genome-wide cell-free (cfDNA) fragmentomes, including fragmentation profiles and repeat landscapes, from the plasma of individuals with (n=148) or without (n=357) brain cancer. Machine learning analyses of cfDNA fragmentome features detected brain cancer across all grade gliomas (AUC=0.90, 95% CI: 0.87-0.93) and these results were validated in an independent prospectively collected cohort. cfDNA fragmentome changes in patients with gliomas represented a combination of fragmentation profiles from glioma cells and altered white blood cell populations in the circulation. These analyses reveal the properties of cfDNA in patients with brain cancer and open new avenues for noninvasive detection of these individuals.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"222 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889324","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

Response and Resistance to RAS Inhibition in Cancer 肿瘤对RAS抑制的反应和抵抗

IF 28.2 1区医学

Cancer discovery Pub Date : 2025-04-28 DOI: 10.1158/2159-8290.cd-25-0349

Richard Y. Ebright, Julien Dilly, Alice T. Shaw, Andrew J. Aguirre

引用次数: 0