Pub Date : 2026-02-03DOI: 10.1158/2159-8290.cd-nw2026-0010
Morning administration of checkpoint inhibitors significantly extended survival in patients with advanced non–small cell lung cancer, in the first randomized trial of immunotherapy timing. The results provide prospective support for aligning treatment with circadian biology as a simple way to improve cancer outcomes.
{"title":"Randomized Trial Links Time of Day to Immunotherapy Success","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0010","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0010","url":null,"abstract":"Morning administration of checkpoint inhibitors significantly extended survival in patients with advanced non–small cell lung cancer, in the first randomized trial of immunotherapy timing. The results provide prospective support for aligning treatment with circadian biology as a simple way to improve cancer outcomes.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"19 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109894","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}
Pub Date : 2026-02-03DOI: 10.1158/2159-8290.cd-nw2026-0009
Five-year data from the phase IIb KEYNOTE-942 study show that the mRNA-based neoantigen vaccine intismeran autogene continues to reduce the risk of melanoma recurrence or death by roughly 49% when combined with pembrolizumab. This durability strengthens confidence in the personalized vaccine strategy, but a larger phase III trial will provide the decisive findings.
{"title":"Personalized Cancer Vaccine Shows Durable Benefit at 5 Years","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0009","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0009","url":null,"abstract":"Five-year data from the phase IIb KEYNOTE-942 study show that the mRNA-based neoantigen vaccine intismeran autogene continues to reduce the risk of melanoma recurrence or death by roughly 49% when combined with pembrolizumab. This durability strengthens confidence in the personalized vaccine strategy, but a larger phase III trial will provide the decisive findings.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"15 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109895","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}
Pub Date : 2026-01-30DOI: 10.1158/2159-8290.cd-25-0859
Tomohiro Aoki,Gerben Duns,Shinya Rai,Aixiang Jiang,Andrew Lytle,Yifan Yin,Makoto Kishida,Michael Yu Li,Cecilia Lee,Denise Smorra,Laura K Hilton,Shannon Healy,Stefan K Alig,Mohammad Shahrokh Esfahani,Clementine Sarkozy,Stacy S Hung,Katy Milne,Adele Telenius,Luke O Brien,Jasper Ch Wong,Claudia Cassidy,Manabu Fujisawa,Celia Strong,Talia Goodyear,Chantal Di Vito,Cassandra Luksik,Glenn Edin,Laura Gonzalez,Juan Rangel Patiño,Michael Hong,Shaocheng Wu,Eric Lee,Ali Sakhdari,Katsuyoshi Takata,Tomoko Miyata-Takata,Merrill Boyle,Susana Ben-Neriah,Andrew P Weng,Alexander Xu,Akil Merchant,Andrew Roth,Michael Crump,John Kuruvilla,Anca Prica,Robert Kridel,David G Huntsman,Brad H Nelson,Pedro Farinha,Ryan D Morin,Ash A Alizadeh,Kerry J Savage,David W Scott,Christian Steidl
The tissue architecture of classic Hodgkin Lymphoma (CHL) is unique among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that co-evolve with a complex ecosystem of immune cells in the tumor microenvironment (TME). The lack of a comprehensive systems-level interrogation has hindered the description of disease heterogeneity and clinically relevant molecular subtypes. Here, we employed an integrative, multimodal approach to characterize CHL tumors using malignant cell sequencing, spatial transcriptomics and imaging mass cytometry. We identified four molecular subtypes (CST, CN913, STB, and CN2P), each characterized by distinct clinical features, mutational patterns, malignant cell gene expression profiles, and spatial architecture involving immune cell populations. Functional modeling of CSF2RB mutations, a characteristic feature of the CST subtype, revealed dysregulated oncogenic signaling and unique TME crosstalk. These findings highlight the significance of multi-dimensional profiling in elucidating patterns of molecular alterations that drive immune ecosystems and underlie therapeutically exploitable vulnerabilities.
{"title":"Multidimensional Characterization of Tumor-Immune Architecture Reveals Clinically Relevant Classic Hodgkin Lymphoma Subtypes.","authors":"Tomohiro Aoki,Gerben Duns,Shinya Rai,Aixiang Jiang,Andrew Lytle,Yifan Yin,Makoto Kishida,Michael Yu Li,Cecilia Lee,Denise Smorra,Laura K Hilton,Shannon Healy,Stefan K Alig,Mohammad Shahrokh Esfahani,Clementine Sarkozy,Stacy S Hung,Katy Milne,Adele Telenius,Luke O Brien,Jasper Ch Wong,Claudia Cassidy,Manabu Fujisawa,Celia Strong,Talia Goodyear,Chantal Di Vito,Cassandra Luksik,Glenn Edin,Laura Gonzalez,Juan Rangel Patiño,Michael Hong,Shaocheng Wu,Eric Lee,Ali Sakhdari,Katsuyoshi Takata,Tomoko Miyata-Takata,Merrill Boyle,Susana Ben-Neriah,Andrew P Weng,Alexander Xu,Akil Merchant,Andrew Roth,Michael Crump,John Kuruvilla,Anca Prica,Robert Kridel,David G Huntsman,Brad H Nelson,Pedro Farinha,Ryan D Morin,Ash A Alizadeh,Kerry J Savage,David W Scott,Christian Steidl","doi":"10.1158/2159-8290.cd-25-0859","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-0859","url":null,"abstract":"The tissue architecture of classic Hodgkin Lymphoma (CHL) is unique among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that co-evolve with a complex ecosystem of immune cells in the tumor microenvironment (TME). The lack of a comprehensive systems-level interrogation has hindered the description of disease heterogeneity and clinically relevant molecular subtypes. Here, we employed an integrative, multimodal approach to characterize CHL tumors using malignant cell sequencing, spatial transcriptomics and imaging mass cytometry. We identified four molecular subtypes (CST, CN913, STB, and CN2P), each characterized by distinct clinical features, mutational patterns, malignant cell gene expression profiles, and spatial architecture involving immune cell populations. Functional modeling of CSF2RB mutations, a characteristic feature of the CST subtype, revealed dysregulated oncogenic signaling and unique TME crosstalk. These findings highlight the significance of multi-dimensional profiling in elucidating patterns of molecular alterations that drive immune ecosystems and underlie therapeutically exploitable vulnerabilities.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"164 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089062","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}
Pub Date : 2026-01-29DOI: 10.1158/2159-8290.cd-rw2026-015
{"title":"Dual Targeting of TGFβ1 and PD-1 Is Safe and Tolerable in Solid Tumors.","authors":"","doi":"10.1158/2159-8290.cd-rw2026-015","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-rw2026-015","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"2 1","pages":"OF1"},"PeriodicalIF":28.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089063","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}
Pub Date : 2026-01-28DOI: 10.1158/2159-8290.cd-rw2026-014
{"title":"vCATCH Maps Cellular Targets of Cancer Drugs throughout the Entire Body.","authors":"","doi":"10.1158/2159-8290.cd-rw2026-014","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-rw2026-014","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"82 1","pages":"OF1"},"PeriodicalIF":28.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089064","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}
Pub Date : 2026-01-27DOI: 10.1158/2159-8290.cd-nw2026-0008
An AI system powered by structured oncology data matched oncologists' treatment choices in more than 90% of real clinical queries, besting a standard large language model. By focusing on a narrowly defined task-genomics-guided therapy selection-the platform demonstrates a practical pathway for deploying reliable AI tools in precision oncology.
{"title":"AI Matches Treatment Choices in Precision Oncology Tests.","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0008","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0008","url":null,"abstract":"An AI system powered by structured oncology data matched oncologists' treatment choices in more than 90% of real clinical queries, besting a standard large language model. By focusing on a narrowly defined task-genomics-guided therapy selection-the platform demonstrates a practical pathway for deploying reliable AI tools in precision oncology.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"293 1","pages":"OF1"},"PeriodicalIF":28.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056821","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}
Pub Date : 2026-01-22DOI: 10.1158/2159-8290.cd-nw2026-0007
Researchers used a unique base-editing strategy to engineer chimeric-antigen receptor (CAR) T cells that engraft in the host and remain invisible to remaining antibody drugs. Of the 11 patients with T-cell acute lymphoblastic leukemia who received these BE-CAR7 T cells, all had complete morphogenic remission after 28 days, 82% underwent stem-cell transplantation, and 64% remain in remission 3 to 36 months after treatment.
{"title":"Base Editing Might Be Key to CAR T-cell Therapy.","authors":"","doi":"10.1158/2159-8290.cd-nw2026-0007","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-nw2026-0007","url":null,"abstract":"Researchers used a unique base-editing strategy to engineer chimeric-antigen receptor (CAR) T cells that engraft in the host and remain invisible to remaining antibody drugs. Of the 11 patients with T-cell acute lymphoblastic leukemia who received these BE-CAR7 T cells, all had complete morphogenic remission after 28 days, 82% underwent stem-cell transplantation, and 64% remain in remission 3 to 36 months after treatment.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"58 1","pages":"OF1"},"PeriodicalIF":28.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021620","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}
Pub Date : 2026-01-22DOI: 10.1158/2159-8290.cd-rw2026-011
{"title":"Surface Protein AQP5 Is a Functional Marker of Gastric Cancer Stem Cells.","authors":"","doi":"10.1158/2159-8290.cd-rw2026-011","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-rw2026-011","url":null,"abstract":"","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"51 1","pages":"OF1"},"PeriodicalIF":28.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056389","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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