Nature Medicine最新文献

{"title":"Early detection of multiple cancer types using multidimensional cell-free DNA fragmentomics","authors":"Hua Bao, Shanshan Yang, Xiaoxi Chen, Guangqiang Dong, Yuan Mao, Shuyu Wu, Xi Cheng, Xuxiaochen Wu, Wanxiangfu Tang, Min Wu, Shiting Tang, Wenhua Liang, Zheng Wang, Liu Yang, Jiaqi Liu, Tao Wang, Bingzhong Zhang, Kuirong Jiang, Qin Xu, Jierong Chen, Hairong Huang, Junjie Peng, Xiaomeng Xia, Yumei Wu, Shun Xu, Ji Tao, Li Chong, Dongqin Zhu, Ruowei Yang, Shuang Chang, Peng He, Xiuxiu Xu, JinPeng Zhang, Yi Shen, Ya Jiang, Sisi Liu, Xian Zhang, Xue Wu, Xiaonan Wang, Yang Shao","doi":"10.1038/s41591-025-03735-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03735-2","url":null,"abstract":"<p>The multicancer early detection (MCED) test has the potential to enhance current cancer-screening methods. We evaluated a new MCED test that analyzes plasma cell-free DNA using genetic- and fragmentomics-based features from whole-genome sequencing. The present study included an internal validation cohort of 3,021 patients with cancer and 3,370 noncancer controls, and an independent cohort of 677 patients with cancer and 687 noncancer individuals. The results demonstrated an overall sensitivity of 87.4%, specificity of 97.8% and tissue-of-origin prediction accuracy of 82.4% in the independent validation cohort. Preliminary results from a prospective study of 3,724 asymptomatic participants showed a sensitivity of 53.5% (predominantly early stage cancers) and specificity of 98.1%. These findings indicate that the MCED test has strong potential to improve early cancer detection and support clinical decision-making.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"34 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145613","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}

{"title":"Lutetium-177–PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial","authors":"Edmond M. Kwan, Sarah W. S. Ng, Sofie H. Tolmeijer, Louise Emmett, Shahneen Sandhu, James P. Buteau, Amir Iravani, Anthony M. Joshua, Roslyn J. Francis, Vinod Subhash, Sze-Ting Lee, Andrew M. Scott, Andrew J. Martin, Martin R. Stockler, Gráinne Donnellan, Matti Annala, Cameron Herberts, Ian D. Davis, Michael S. Hofman, Arun A. Azad, Alexander W. Wyatt","doi":"10.1038/s41591-025-03704-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03704-9","url":null,"abstract":"<p>The prostate-specific membrane antigen (PSMA)-targeted radioligand [¹⁷⁷Lu]Lu–PSMA-617 is a new standard treatment for metastatic castration-resistant prostate cancer (mCRPC), but predictive genomic biomarkers informing its rational use are unknown. We performed detailed dissection of prostate cancer driver genes across 290 serial plasma cell-free DNA samples from 180 molecular imaging-selected patients with mCRPC from the randomized TheraP trial of [¹⁷⁷Lu]Lu–PSMA-617 (<i>n</i> = 97) versus cabazitaxel chemotherapy (<i>n</i> = 83). The primary endpoint was PSA50 biochemical response, with secondary endpoints of progression-free survival (PFS) and overall survival (OS). In this post-hoc biomarker analysis, a low pretreatment circulating tumor DNA (ctDNA) fraction predicted a superior biochemical response (100% versus 58%, <i>P</i> = 0.0067) and PFS (median 14.7 versus 6.0 months; hazard ratio 0.12, <i>P</i> = 2.5 × 10⁻⁴) on [¹⁷⁷Lu]Lu–PSMA-617 independent of predictive PSMA–positron emission tomography imaging parameters, although this benefit did not extend to OS. Deleterious <i>PTEN</i> alterations were associated with worse PFS and OS on cabazitaxel, whereas <i>ATM</i> defects were observed in select patients with favorable [¹⁷⁷Lu]Lu–PSMA-617 outcomes. Comparing pretreatment and progression ctDNA revealed population flux but no evidence that alterations in individual mCRPC genes (or <i>FOLH1</i>) are dominant causes of acquired [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel resistance. Our results nominate new candidate biomarkers for [¹⁷⁷Lu]Lu–PSMA-617 selection and ultimately expand the mCRPC predictive biomarker repertoire. We anticipate our ctDNA fraction-aware analytical framework will aid future precision management strategies for [¹⁷⁷Lu]Lu–PSMA-617 and other PSMA-targeted therapeutics. ClinicalTrials.gov identifier: NCT03392428.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"133 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145615","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}

{"title":"Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial","authors":"Michael Grimley, Stella M. Davies, Archana Shrestha, Amy Shova, Monika Asnani, Michael Kent, Farzana Sayani, Charles T. Quinn, Omar Niss, Carolyn Lutzko, Parinda A. Mehta, Pooja Khandelwal, Courtney Little, Sharat Chandra, Sydney Felker, Mengna Chi, Theodosia A. Kalfa, Jennifer Knight-Madden, Paritha I. Arumugam, Kristie N. Ramos, Scott Witting, Teresa Latham, Frederic D. Bushman, Punam Malik","doi":"10.1038/s41591-025-03662-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03662-2","url":null,"abstract":"<p>Autologous transplantation of gene-modified cells for treatment of sickle cell disease has involved myeloablative conditioning with associated cytopenias and toxicities. We report results of seven patients treated in a first-in-human phase 1/2 study for sickle cell disease using reduced-intensity conditioning transplant of autologous hematopoietic stem cells genetically modified with a lentiviral vector (GbG^M), with 2–7 yr of follow-up. GbG^M encodes a modified γ-globin gene that expresses a potent anti-sickling fetal hemoglobin, HbF^G16D. The primary study objectives were safety (occurrence of adverse events and duration of neutropenia and thrombocytopenia) and feasibility of treatment. Primary feasibility endpoints of collection of at least 8 × 10⁶ CD34⁺ cells per kg body weight, successful transduction of a minimum of 4 × 10⁶ CD34⁺ cells per kg body weight and the number of subjects with an average vector copy number of &gt;0.01 copies per cell 1 yr after infusion were met. A median of 4 collections (range, 4–8) were needed to achieve the target cell dose, and all products achieved the target vector copy number. There were 503 adverse events in the seven patients throughout the study period, the most common being grade 2–3 vaso-occlusive crisis. Median duration of grade 4 thrombocytopenia was 5 d and of grade 4 neutropenia was 8 d. All seven patients exhibited sustained HbF^G16D expression and &gt;80% reduction in severe vaso-occlusive events (secondary endpoints). The clinical trial was terminated after infusion of the seventh patient as the predetermined primary endpoints were met and industry funding was complete. Larger trials are warranted to evaluate the benefits of reduced-intensity conditioning. ClinicalTrials.gov registration number: NCT02186418.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"149 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137195","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}

{"title":"How US politics is undermining global science","authors":"Jeremy W. Jacobs, Garrett S. Booth","doi":"10.1038/s41591-025-03741-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03741-4","url":null,"abstract":"<p>In June 2025, the International Society on Thrombosis and Haemostasis (ISTH) will convene its annual congress in Washington, DC — a gathering that has long exemplified global scientific exchange. However, this year, international attendees are being urged to take unusual precautions. The society’s recent travel guidance advises participants to limit personal data on devices, edit social media profiles, and consult immigration attorneys¹, which align with recommendations from other countries for individuals traveling to the USA². These precautions, although framed as practical, are a sobering indictment of the current political climate in the USA. They suggest a country that is becoming an increasingly hostile environment for international scholars, and is no longer unequivocally committed to open scientific exchange³.</p><p>The USA has historically served as a hub for biomedical research, home to leading academic institutions, National Institute of Health (NIH)-funded laboratories, and major scientific conferences. However, the very infrastructure that sustains global scientific cooperation is being threatened by rising political nationalism, suspicion of foreign influence, and the weaponization of immigration enforcement⁴. These shifts are not merely bureaucratic — they are ideological, and they are redefining who is permitted to participate in the scientific enterprise.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"155 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122774","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}

{"title":"Surgery avoidable with immunotherapy in mismatch repair-deficient tumors","authors":"","doi":"10.1038/d41591-025-00033-9","DOIUrl":"https://doi.org/10.1038/d41591-025-00033-9","url":null,"abstract":"In a phase 2 trial, complete responses to neoadjuvant dostarlimab allowed most patients with early-stage solid tumors to avoid surgery, which allowed preservation of affected organs.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"4 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122775","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}

{"title":"Cancer treatment paradigms in the precision medicine era","authors":"Vivek Subbiah, Giuseppe Curigliano, Jason K. Sicklick, Shumei Kato, Kjetil Tasken, Arielle Medford, Damian T. Rieke, Hui-Zi Chen, Adam Wahida, Lars Buschhorn, Denis Horgan, Razelle Kurzrock","doi":"10.1038/s41591-025-03711-w","DOIUrl":"https://doi.org/10.1038/s41591-025-03711-w","url":null,"abstract":"To fully harness precision medicine and transform cancer care for the better will require a strategic shift to highly personalized interventions that embrace innovation and adaptability.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"25 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097145","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}

{"title":"Nutrition research must go local","authors":"","doi":"10.1038/s41591-025-03748-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03748-x","url":null,"abstract":"Understanding the health impacts of local, culturally relevant diets will be critical to advancing precision nutrition across diverse populations in a sustainable way.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"4 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097144","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}

{"title":"Author Correction: Prediction of mental health risk in adolescents","authors":"Elliot D. Hill, Pratik Kashyap, Elizabeth Raffanello, Yun Wang, Terrie E. Moffitt, Avshalom Caspi, Matthew Engelhard, Jonathan Posner","doi":"10.1038/s41591-025-03769-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03769-6","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-025-03560-7, published online 5 March 2025.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"18 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097146","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}

{"title":"Addendum: Sensitive in vivo imaging of T cells using a membrane-bound Gaussia princeps luciferase","authors":"Elmer B Santos, Raymond Yeh, James Lee, Yan Nikhamin, Blesida Punzalan, Blesserene Punzalan, Krista La Perle, Steven M Larson, Michel Sadelain, Renier J Brentjens","doi":"10.1038/s41591-025-03761-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03761-0","url":null,"abstract":"<p>Addendum to: <i>Nature Medicine</i> https://doi.org/10.1038/nm.1930, published online 15 February 2009.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"40 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097286","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}

{"title":"Using metformin to stall clonal hematopoiesis","authors":"","doi":"10.1038/d41591-025-00032-w","DOIUrl":"https://doi.org/10.1038/d41591-025-00032-w","url":null,"abstract":"Three translational studies reveal elevated mitochondrial metabolism as a driver of age-related clonal hematopoiesis and suggest that targeting this process — for example, with metformin — could reduce the risk of associated diseases.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"34 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067095","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}