Pub Date : 2026-01-29DOI: 10.1038/d41573-025-00187-8
Amanda Klein,Jeffrey Siegel,Steve Hoffmann,Jennifer D Hamilton,Hearn Jay Cho,Douglas R Lowy,John A Wagner
{"title":"The Biomarkers Consortium: 20 years of advancing precision medicine.","authors":"Amanda Klein,Jeffrey Siegel,Steve Hoffmann,Jennifer D Hamilton,Hearn Jay Cho,Douglas R Lowy,John A Wagner","doi":"10.1038/d41573-025-00187-8","DOIUrl":"https://doi.org/10.1038/d41573-025-00187-8","url":null,"abstract":"","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-28DOI: 10.1038/s41573-025-01364-5
Peter C Searson,William A Banks
Blood-brain barrier (BBB) dysfunction is a hallmark of many diseases of the brain, including those that represent the largest healthcare burden (for example, Alzheimer disease and stroke). Despite this, rejuvenation and repair of the BBB is not a mainstream concept. During life, the BBB is subjected to perturbations and stresses from a wide range of endogenous or exogenous sources, which can promote brain health or can lead to brain pathologies. The BBB supports many functions that are critical for central nervous system homeostasis and so there are many mechanisms of dysfunction, and hence many targets for intervention. Furthermore, many mechanisms are shared among diseases and disease subtypes, resulting in the potential for common strategies for BBB repair. In this Review, we consider the BBB as a therapeutic target and discuss approaches to its repair and protection in specific disease states and during normal ageing.
{"title":"Strategies for blood-brain barrier rejuvenation and repair.","authors":"Peter C Searson,William A Banks","doi":"10.1038/s41573-025-01364-5","DOIUrl":"https://doi.org/10.1038/s41573-025-01364-5","url":null,"abstract":"Blood-brain barrier (BBB) dysfunction is a hallmark of many diseases of the brain, including those that represent the largest healthcare burden (for example, Alzheimer disease and stroke). Despite this, rejuvenation and repair of the BBB is not a mainstream concept. During life, the BBB is subjected to perturbations and stresses from a wide range of endogenous or exogenous sources, which can promote brain health or can lead to brain pathologies. The BBB supports many functions that are critical for central nervous system homeostasis and so there are many mechanisms of dysfunction, and hence many targets for intervention. Furthermore, many mechanisms are shared among diseases and disease subtypes, resulting in the potential for common strategies for BBB repair. In this Review, we consider the BBB as a therapeutic target and discuss approaches to its repair and protection in specific disease states and during normal ageing.","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-26DOI: 10.1038/s41573-025-01349-4
Jérôme Avouac, Adi Barzel, Delma Caiati, Randall S. Davis, Stephen Gottschalk, Ricardo Grieshaber-Bouyer, Xuming Mao, Eline T. Luning Prak, Marko Radic, Marc Scherlinger, Yatin Suneja, Aimee Talleur, Amber L. Thacker, Derya Unutmaz
{"title":"Roads and detours for CAR T cell therapy in autoimmune diseases","authors":"Jérôme Avouac, Adi Barzel, Delma Caiati, Randall S. Davis, Stephen Gottschalk, Ricardo Grieshaber-Bouyer, Xuming Mao, Eline T. Luning Prak, Marko Radic, Marc Scherlinger, Yatin Suneja, Aimee Talleur, Amber L. Thacker, Derya Unutmaz","doi":"10.1038/s41573-025-01349-4","DOIUrl":"https://doi.org/10.1038/s41573-025-01349-4","url":null,"abstract":"","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1038/s41573-025-01336-9
Teemu Haikarainen,Anniina T Virtanen,Benjamin F Cravatt,Olli Silvennoinen
Type I/II cytokine receptors mediate cytokine-specific biological responses by employing a defined combination of four Janus kinases (JAKs) and seven signal transducers and activators of transcription (STATs) for cellular signal transduction. Deregulation of the JAK-STAT pathway leads to various diseases, with JAK and STAT proteins representing attractive therapeutic targets. Fifteen JAK inhibitors are approved for several immunological and haematological diseases, offering significant benefits for patients. However, safety restrictions have limited their clinical use. Mechanistic and structural insights are driving current drug development approaches focused on improving their potency, selectivity and safety. Development of STAT inhibitors has been more challenging, and none has yet received clinical approval, although promising new compounds are now entering clinical trials. This Review discusses the recent advances in JAK and STAT inhibitor development and presents emerging therapeutic indications for JAK-STAT inhibition.
{"title":"Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.","authors":"Teemu Haikarainen,Anniina T Virtanen,Benjamin F Cravatt,Olli Silvennoinen","doi":"10.1038/s41573-025-01336-9","DOIUrl":"https://doi.org/10.1038/s41573-025-01336-9","url":null,"abstract":"Type I/II cytokine receptors mediate cytokine-specific biological responses by employing a defined combination of four Janus kinases (JAKs) and seven signal transducers and activators of transcription (STATs) for cellular signal transduction. Deregulation of the JAK-STAT pathway leads to various diseases, with JAK and STAT proteins representing attractive therapeutic targets. Fifteen JAK inhibitors are approved for several immunological and haematological diseases, offering significant benefits for patients. However, safety restrictions have limited their clinical use. Mechanistic and structural insights are driving current drug development approaches focused on improving their potency, selectivity and safety. Development of STAT inhibitors has been more challenging, and none has yet received clinical approval, although promising new compounds are now entering clinical trials. This Review discusses the recent advances in JAK and STAT inhibitor development and presents emerging therapeutic indications for JAK-STAT inhibition.","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1038/d41573-025-00208-6
Heather Bowling,Arianna Cocucci,Da Chen Emily Koo,Richard K Harrison
{"title":"Analysis of phase II and phase III clinical trial terminations from 2013 to 2023.","authors":"Heather Bowling,Arianna Cocucci,Da Chen Emily Koo,Richard K Harrison","doi":"10.1038/d41573-025-00208-6","DOIUrl":"https://doi.org/10.1038/d41573-025-00208-6","url":null,"abstract":"","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1038/s41573-025-01323-0
Elizabeth A. Heller, Lacramioara Bintu, Marianne G. Rots
{"title":"Epigenetic editing: from concept to clinic","authors":"Elizabeth A. Heller, Lacramioara Bintu, Marianne G. Rots","doi":"10.1038/s41573-025-01323-0","DOIUrl":"https://doi.org/10.1038/s41573-025-01323-0","url":null,"abstract":"","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"191 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1038/s41573-025-01317-y
Daisong Wang, Remi Villenave, Nadine Stokar-Regenscheit, Hans Clevers
{"title":"Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges","authors":"Daisong Wang, Remi Villenave, Nadine Stokar-Regenscheit, Hans Clevers","doi":"10.1038/s41573-025-01317-y","DOIUrl":"https://doi.org/10.1038/s41573-025-01317-y","url":null,"abstract":"","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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