Nature Medicine最新文献

{"title":"Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial","authors":"Matthias Preusser, Javier Garde-Noguera, Juan José García-Mosquera, María Gion, Richard Greil, Miriam Arumi, Manuel Ruiz-Borrego, Antonio Llombart-Cussac, María Valero, Javier Cortés, Marta Campolier, José Antonio Guerrero, Paula González-Alonso, Carlos Jiménez-Cortegana, Jose Rodríguez-Morató, Marta Vaz-Batista, Felicitas Oberndorfer, Maximilian Marhold, Anna Sophie Berghoff, Julia Furtner, Thorsten Fuereder, Rupert Bartsch","doi":"10.1038/s41591-025-03744-1","DOIUrl":"https://doi.org/10.1038/s41591-025-03744-1","url":null,"abstract":"<p>Leptomeningeal metastatic disease (LMD) is a severe complication of solid cancers with poor outcomes and limited treatment options. The antibody–drug conjugate patritumab deruxtecan (HER3-DXd) demonstrated efficacy in breast and lung cancers, and HER3 is involved in central nervous system metastases, particularly in parenchymal colonization. In this study, we investigated HER3-DXd efficacy and safety in patients with LMD in cohort 3 of the TUXEDO-3 phase 2 trial. Key eligibility criteria included age ≥18 years, treatment-naive LMD or LMD progressing after radiotherapy from any solid tumor and Eastern Cooperative Oncology Group performance status of 0–2. Between January and July 2024, 20 evaluable patients (nine with type I and 11 with type II LMD) were accrued and received HER3-DXd 5.6 mg kg⁻¹ intravenously every 3 weeks. Main primary tumor types included breast (60%) and lung (30%) cancers. Median follow-up time was 5.4 months. The primary endpoint was met with 65.0% patients alive after 3 months. The Kaplan–Meier-estimated 3-month and 6-month overall survival rates were 69.6% and 58.9%, respectively. Overall response rate was 11.1% for intracranial, 30.8% for extracranial and 26.3% for overall lesions. Clinical benefit rate was 50.0% for intracranial, 38.5% for extracranial and 47.4% for overall lesions. Neurological symptoms and quality of life remained stable or improved during study treatment. No new neurological adverse events were observed. The most common adverse events of any grade were anemia (nine (40.9%) patients, one (4.5%) grade ≥3), nausea (seven (31.8%) patients, no grade ≥3), neutropenia (six (27.3%) patients, three (13.6%) grade ≥3), diarrhea (six (27.3%) patients, one (4.5%) grade ≥3), asthenia (six (27.3%) patients, no grade ≥3) and thrombocytopenia and headache (five (22.7%) patients, one (4.5%) grade ≥3 each). TUXEDO-3 showed clinically relevant HER3-DXd activity in patients with LMD. ClinicalTrials.gov identifier: NCT05865990.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"28 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184112","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 to sustain a public-health genomics and bioinformatics workforce in Africa","authors":"Harris Onywera, Nicola Mulder, Yenew Kebede, Sofonias K. Tessema","doi":"10.1038/s41591-025-03720-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03720-9","url":null,"abstract":"African countries have made progress in expanding their genomics and bioinformatics workforces for public health, yet several barriers pose risks to workforce retention and long-term sustainability.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"147 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165355","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":"Hyperimmune volunteer enables discovery of a potent snake antivenom","authors":"","doi":"10.1038/d41591-025-00035-7","DOIUrl":"https://doi.org/10.1038/d41591-025-00035-7","url":null,"abstract":"Researchers studied the antibody library of a venom-immune person with extensive snakebite exposure — and generated a three-agent, broadly neutralizing cocktail that protected mice against venoms from high-priority species.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"134 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165354","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":"Semaglutide treats MASH liver disease","authors":"","doi":"10.1038/d41591-025-00034-8","DOIUrl":"https://doi.org/10.1038/d41591-025-00034-8","url":null,"abstract":"GLP-1 receptor agonist semaglutide significantly outperformed placebo in an ongoing phase 3 trial, showing reductions in steatohepatitis and liver fibrosis, in addition to cardiometabolic benefits.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"13 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165353","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":"Rebuilding global health after the demise of USAID","authors":"Charles Coughlan, Arpan R. Mehta","doi":"10.1038/s41591-025-03766-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03766-9","url":null,"abstract":"<p>Many commentators anticipated a downturn in the fortunes of the United States Agency of International Development (USAID) after the re-election of President Trump. Nonetheless, its abrupt demise has sent shockwaves through low- and middle-income countries (LMICs). Optimists may hope that this is a Trumpian flash in the pan, which will be quickly reversed with a change in government. However, overseas development assistance (ODA) cuts announced by the British, French and German governments suggest that this is an inflection point for global health.</p><p>In the short term, affected LMICs will need to respond to substantial budget cuts. This may necessitate the withdrawal of effective services — an unpopular move, which risks political difficulty for local and national governments, further sowing global instability. In the medium term, multilateral institutions are due for funding replenishment in the next 1–2 years. The USA has historically provided around one-sixth of total funding to Gavi, the Vaccine Alliance¹, and one-third of pledges to the Global Fund to Fight AIDS, Tuberculosis and Malaria². Without prompt action to meet anticipated funding gaps, an extra 14.9 million malaria cases and 107,000 deaths could occur in 2025 alone³. Countless vaccine-preventable childhood deaths are estimated to follow in the next decade.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"82 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165484","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":"Molecular determinants of sotorasib clinical efficacy in KRASG12C-mutated non-small-cell lung cancer","authors":"Ferdinandos Skoulidis, Bob T. Li, Adrianus Johannes de Langen, David S. Hong, Herve Lena, Juergen Wolf, Grace K. Dy, Alessandra Curioni Fontecedro, Pascale Tomasini, Vamsidhar Velcheti, Anthonie J. van der Wekken, Christophe Dooms, Luis Paz-Ares Rodriguez, Giannis Mountzios, Adrian Sacher, Ernest Nadal, Sebastien Couraud, Sang-We Kim, Kenneth O’Byrne, Danilo Rocco, Ryo Toyozawa, Izabela Chmielewska, Colin R. Lindsay, Antreas Hindoyan, Lata Mukundan, Tomasz Wilmanski, Abraham Anderson, Christine Ardito-Abraham, Amrita Pati, Anita Reddy, Bhakti Mehta, Martin Schuler","doi":"10.1038/s41591-025-03732-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03732-5","url":null,"abstract":"<p>Molecular determinants of KRAS(G12C)inhibitor efficacy in <i>KRAS</i>^<i>G12C</i>-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized. Here we report one of the largest integrated analyses to date of sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 studies. We reveal differential sotorasib activity and relative benefit compared to docetaxel across <i>KRAS</i>^<i>G12C</i>-mutated NSCLC co-mutational subsets and transcriptional subtypes. We also identify low expression of <i>TTF1</i> and <i>KEAP1</i> co-mutations/NRF2 activation as major determinants of sotorasib anti-tumor efficacy and adverse prognostic features. Exploratory analyses highlight potential tumor cell-extrinsic contributors to sotorasib anti-tumor activity and suggest that early on-treatment clearance of <i>KRAS</i>^<i>G12C</i>- circulating tumor DNA may refine clinical response prediction algorithms. Our findings advance precision medicine for patients with <i>KRAS</i>^<i>G12C</i>-mutated NSCLC and establish a framework for patient stratification and selection for treatment intensification with rationally applied therapeutic combinations.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"3 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153361","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":"Lifeline: a musical about antimicrobial resistance that raises awareness and inspires action","authors":"Jaime Garcia-Iglesias, Katharine Relph, Robin Hiley, Jess Conway, Graham Richardson, Mary Stahl, Claire Oxlade, Rebecca Murphy-Hoefer, CarriAyne Jones, Meghan Perry","doi":"10.1038/s41591-025-03736-1","DOIUrl":"https://doi.org/10.1038/s41591-025-03736-1","url":null,"abstract":"<p>“Future generations must take on this responsibility to protect antibiotics at all costs. Before it is too late”. These are the words of Alexander Fleming’s character in the 2024 version of the musical <i>Lifeline</i>.</p><p>Antimicrobial resistance (AMR) is a growing global crisis. The bleak statistics that estimated 4.71 million deaths associated with AMR worldwide in 2021¹ require shifts in attitudes and behaviors towards antibiotics that can be challenging to implement. The World Health Organization (WHO) recently published a people-centered approach to addressing AMR with a key foundational step of effective governance, awareness and education within the healthcare sector and the general public². Here we show that a strategy to support this is by using creative arts, storytelling and the generation of emotional responses to promote behavioral change³.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"35 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153359","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":"Implementing digital health to support self-care of chronic diseases","authors":"Marie Löf, Ralph Maddison","doi":"10.1038/s41591-025-03729-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03729-0","url":null,"abstract":"Here we propose six recommendations for researchers to consider for the successful implementation of evidence-based digital health interventions into routine clinical practice.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"34 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153360","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":"Patient-centered integration of tumor and germline genetic results can improve cancer care","authors":"Alanna J. Church, Oindrila Bhattacharyya, Julie O. Culver, Yonatan Amzaleg, Erin Linnenbringer, Maeve Smart, Christina Ip-Toma, Adan Reinosa Rivera, Bethany Davis, Charité Ricker, Heinz-Josef Lenz, Stacy W. Gray, Heather Hampel, David W. Craig","doi":"10.1038/s41591-025-03686-8","DOIUrl":"https://doi.org/10.1038/s41591-025-03686-8","url":null,"abstract":"Germline sequencing should be integrated with somatic testing of cancers to provide a comprehensive genetic assessment of disease.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"40 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145822","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":"Feasibility of multiomics tumor profiling for guiding treatment of melanoma","authors":"Nicola Miglino, Nora C. Toussaint, Alexander Ring, Ximena Bonilla, Marina Tusup, Benedict Gosztonyi, Tarun Mehra, Gabriele Gut, Francis Jacob, Stephane Chevrier, Kjong-Van Lehmann, Ruben Casanova, Andrea Jacobs, Sujana Sivapatham, Laura Boos, Parisa Rahimzadeh, Manuel Schuerch, Bettina Sobottka, Natalia Chicherova, Shuqing Yu, Rebekka Wegmann, Julien Mena, Emanuela S. Milani, Sandra Goetze, Cinzia Esposito, Jacobo Sarabia del Castillo, Anja L. Frei, Marta Nowak, Anja Irmisch, Jack Kuipers, Monica-Andreea Baciu-Drăgan, Pedro F. Ferreira, Franziska Singer, Anne Bertolini, Michael Prummer, Ulrike Lischetti, Rudolf Aebersold, Marina Bacac, Gerd Maass, Holger Moch, Michael Weller, Alexandre P. A. Theocharides, Markus G. Manz, Niko Beerenwinkel, Christian Beisel, Lucas Pelkmans, Berend Snijder, Bernd Wollscheid, Viola Heinzelmann, Bernd Bodenmiller, Mitchell P. Levesque, Viktor H. Koelzer, Gunnar Rätsch, Reinhard Dummer, Andreas Wicki","doi":"10.1038/s41591-025-03715-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03715-6","url":null,"abstract":"<p>There is limited evidence supporting the feasibility of using omics and functional technologies to inform treatment decisions. Here we present results from a cohort of 116 melanoma patients in the prospective, multicentric observational Tumor Profiler (TuPro) precision oncology project. Nine independent technologies, mostly at single-cell level, were used to analyze 126 patient samples, generating up to 500 Gb of data per sample (40,000 potential markers) within 4 weeks. Among established and experimental markers, the molecular tumor board selected 54 to inform its treatment recommendations. In 75% of cases, TuPro-based data were judged to be useful in informing recommendations. Patients received either standard of care (SOC) treatments or highly individualized, polybiomarker-driven treatments (beyond SOC). The objective response rate in difficult-to-treat palliative, beyond SOC patients (<i>n</i> = 37) was 38%, with a disease control rate of 54%. Progression-free survival of patients with TuPro-informed therapy decisions was 6.04 months, (95% confidence interval, 3.75–12.06) and 5.35 months (95% confidence interval, 2.89–12.06) in ≥third therapy lines. The proof-of-concept TuPro project demonstrated the feasibility and relevance of omics-based tumor profiling to support data-guided clinical decision-making. ClinicalTrials.gov identifier: NCT06463509.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"51 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145823","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}