发布求助
文献互助 智能选刊 最新文献

Cancer discovery最新文献

筛选
英文 中文
MANIFEST: Multiomic Platform for Cancer Immunotherapy. MANIFEST：癌症免疫治疗的多组学平台。
IF 28.2 1区 医学
Cancer discovery Pub Date : 2025-05-02 DOI: 10.1158/2159-8290.cd-25-0099
Kok Haw Jonathan Lim,Zayd Tippu,Pippa G Corrie,Michael Hubank,James Larkin,Trevor D Lawley,Mark Stares,Grant D Stewart,Amy Strange,Stefan N Symeonides,Bernadett Szabados,Nicholas C Turner,Tom Waddell,Santiago Zelenay,Manuel Salto-Tellez,Caroline Dive,Samra Turajlic,
{"title":"MANIFEST: Multiomic Platform for Cancer Immunotherapy.","authors":"Kok Haw Jonathan Lim,Zayd Tippu,Pippa G Corrie,Michael Hubank,James Larkin,Trevor D Lawley,Mark Stares,Grant D Stewart,Amy Strange,Stefan N Symeonides,Bernadett Szabados,Nicholas C Turner,Tom Waddell,Santiago Zelenay,Manuel Salto-Tellez,Caroline Dive,Samra Turajlic,","doi":"10.1158/2159-8290.cd-25-0099","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0099","url":null,"abstract":"Immunotherapy has revolutionized survival outcomes for many patients diagnosed with cancer. However, biomarkers that can reliably distinguish treatment responders from nonresponders, predict potential life-threatening and life-changing drug-induced toxicities, or rationalize treatment choices are still lacking. In response to this unmet clinical need, we introduce Multiomic ANalysis of Immunotherapy Features Evidencing Success and Toxicity, a tumor type-agnostic platform to provide deep profiling of patients receiving immunotherapy that will enable integrative identification of biomarkers and discovery of novel targets using artificial intelligence and machine learning.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"118 1","pages":"878-883"},"PeriodicalIF":28.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902903","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
Prenatal Chemotherapy and Its Impact on the Genome of Fetal Hematopoiesis 产前化疗及其对胎儿造血基因组的影响
IF 28.2 1区 医学
Cancer discovery Pub Date : 2025-05-02 DOI: 10.1158/2159-8290.cd-25-0209
Ken Furudate, Koichi Takahashi
{"title":"Prenatal Chemotherapy and Its Impact on the Genome of Fetal Hematopoiesis","authors":"Ken Furudate, Koichi Takahashi","doi":"10.1158/2159-8290.cd-25-0209","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0209","url":null,"abstract":"Summary: The genotoxic impact of cancer chemotherapy administered during pregnancy on neonatal hematopoietic cells remains largely unknown. In this study, Struys and colleagues demonstrate that prenatal chemotherapy exposure leads to an increased somatic mutational burden in neonatal hematopoietic stem and progenitor cells, characterized by distinct mutational signatures, revealing a previously unrecognized consequence of in utero chemotherapy on fetal hematopoiesis and underscoring the need for further research to assess its long-term implications and potential risks. See related article by Struys et al., p. 903","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"34 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901254","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
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
{"title":"Under (Genetic Selection) Pressure: Human Tumors and Human Populations in Hypoxia.","authors":"Frank S Lee","doi":"10.1158/2159-8290.cd-25-0175","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0175","url":null,"abstract":"Arenillas and colleagues report that pheochromocytomas and paragangliomas in the setting of chronic hypoxia due to cyanotic congenital heart disease harbor, at high frequency, somatic gain-of-function mutations in the EPAS1 gene, which encodes for one of the oxygen-labile subunits of the hypoxia-inducible factor complex. Interestingly, germline loss-of-function EPAS1 alleles are under natural selection in human populations subjected to a different chronic hypoxia condition, namely, high altitude. See related article by Arenillas et al., p. XX.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"11 1","pages":"OF1-OF3"},"PeriodicalIF":28.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893145","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
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
{"title":"FABP4-tastic Pancreatic Stellate Cells Coddle KITL to Uphold Inherent Microenvironmental Tumor Suppression.","authors":"Aleksandr Dolskii,Edna Cukierman","doi":"10.1158/2159-8290.cd-25-0212","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0212","url":null,"abstract":"Oñate and colleagues demonstrate that KITL expression in pancreatic stellate cells is crucial for maintaining the inherent tumor-suppressive function of the pancreatic microenvironment, and its loss enables pancreatic cancer development. This pivotal discovery not only reinforces the century-old hypothesis of natural microenvironmental tumor suppression but also highlights a promising therapeutic avenue whereby restoring KITL expression could reestablish the tumor-suppressive functions of pancreas-resident fibroblastic cells. See related article by Oñate et al., p. XX.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"19 1","pages":"OF1-OF3"},"PeriodicalIF":28.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893143","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-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
{"title":"Cancer-Associated Cachexia: Bridging Clinical Findings with Mechanistic Insights in Human Studies.","authors":"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","doi":"10.1158/2159-8290.cd-25-0293","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0293","url":null,"abstract":"CAC represents a significant clinical unmet need. Despite its high prevalence and associated mortality and morbidity, there are currently no globally approved effective therapies. This review provides a comprehensive overview of human studies aimed at defining CAC clinically and identifying mediators underlying it that are revealing effective health interventions. Furthermore, we highlight ongoing international efforts to advance our understanding of CAC.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"9 1","pages":"OF1-OF26"},"PeriodicalIF":28.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889321","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
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
{"title":"Response and Resistance to RAS Inhibition in Cancer","authors":"Richard Y. Ebright, Julien Dilly, Alice T. Shaw, Andrew J. Aguirre","doi":"10.1158/2159-8290.cd-25-0349","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0349","url":null,"abstract":"RAS inhibition has the potential to transform cancer treatment for many patients. The landscape of RAS inhibitor therapies is rapidly evolving, with two mutant-selective KRAS inhibitors now approved and multiple other mutant-selective, pan-KRAS, and pan-RAS inhibitors in development. However, monotherapy efficacy has been limited by primary and acquired resistance. In this article, we review preclinical and clinical data on RAS inhibition in cancer and describe multiple genetic and nongenetic mechanisms of resistance. Moreover, we highlight future opportunities for the design of rational combination therapy strategies, which will ultimately be needed to overcome resistance and enhance the efficacy of these promising treatments. Significance: RAS inhibitors have shown early evidence of efficacy in multiple cancer types, but clinical benefit is limited by acquired resistance. Development of best-in-class inhibitors, with optimal potency, selectivity, and pharmacokinetic properties, as well as effective and tolerable combination therapies will be needed to overcome resistance and maximize the clinical impact of RAS-targeted therapy.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"47 1","pages":"OF1-OF25"},"PeriodicalIF":28.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884647","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
下一页 尾页
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整，为了账户安全，请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们：info@booksci.cn Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号：481959085
Book学术官方微信