Nature Medicine最新文献

{"title":"Critical evaluation of the ProfiLER-02 study design and outcomes","authors":"Vivek Subbiah, Razelle Kurzrock","doi":"10.1038/s41591-025-03959-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03959-2","url":null,"abstract":"<p><span>arising from</span> Olivier Trédan et al. <i>Nature Medicine</i> https://doi.org/10.1038/s41591-025-03613-x (2025)</p><p>The ProfiLER-02 study, discussed in ref. ¹, represents a significant randomized controlled trial examining genomic testing approaches in cancer treatment. The study compared comprehensive genetic testing (324 genes) versus limited testing (87 genes) in 339 patients with advanced solid tumors to determine which approach yielded better treatment recommendations and clinical outcomes¹. The comprehensive genetic panel demonstrated superior identification of potential treatments, detecting actionable targets in 52% of patients compared to 37% with the smaller panel, a notable 15%-point increase. Additionally, more patients received molecularly-targeted treatments with comprehensive testing (14% versus 9%). However, despite identifying more treatment options, the study found no improvement in patient survival or treatment response rates, highlighting a critical gap between genomic discovery and clinical benefit¹. While this randomized controlled trial represents a valuable effort to provide patients with access to testing, several methodological limitations in its design, implementation and analysis may limit its generalizability and leave important questions for future research to address.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"241 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025479","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":"The power of RNA sequencing in molecular oncology","authors":"","doi":"10.1038/s41591-025-03973-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03973-4","url":null,"abstract":"We assessed the utility of RNA sequencing in molecular diagnostics by analyzing a large pan-cancer cohort ranging in age from infants to seniors. This technique is highly sensitive for the identification of gene alterations that can guide diagnosis and targeted therapy, and enables additional biological and clinical interpretation of findings beyond standard DNA-sequencing protocols.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"15 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017405","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":"The WHO global landscape of cancer clinical trials","authors":"Raffaella Casolino,&nbsp;Lambed Tatah,&nbsp;Sarah Charnaud,&nbsp;Marilina Santero,&nbsp;Andrè Ilbawi,&nbsp;Anna Laura Ross","doi":"10.1038/s41591-025-03926-x","DOIUrl":"10.1038/s41591-025-03926-x","url":null,"abstract":"Clinical trials are essential to advancing cancer control, yet access and participation remain unequal globally. The World Health Organization (WHO) established the International Clinical Trials Registry Platform (ICTRP) to enable a complete view of interventional clinical research for all those involved in healthcare decision-making and to identify actionable goals to equitable participation at the global level. A review of 89,069 global cancer clinical trials registered in the WHO ICTRP between 1999 and December 2022 revealed a cancer clinical trial landscape dominated by high-income countries and focused on pharmacological interventions, with multinational collaboration limited to only 3% of recruiting trials. Several of the deadliest cancers, including liver, stomach, pancreas and cervical cancer, were consistently missing from the top most-studied cancer types, particularly in Africa and Southeast Asia. In this Review, we summarize the key findings of the WHO global landscape review and discuss strategies to act on these data, which provide critical empirical evidence to inform policy, practice and investment decisions. This Review of the WHO’s International Clinical Trials Registry Platform presents a snapshot of the global cancer trial landscape and provides critical empirical evidence to inform policy, practice and investment.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 9","pages":"2901-2912"},"PeriodicalIF":50.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-025-03926-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses","authors":"Joshua E. Reuss, Paul K. Lee, Reza J. Mehran, Chen Hu, Suqi Ke, Amna Jamali, Mimi Najjar, Noushin Niknafs, Jaime Wehr, Ezgi Oner, Qiong Meng, Gavin Pereira, Samira Hosseini-Nami, Mark Sausen, Marianna Zahurak, Richard J. Battafarano, Russell K. Hales, Joseph Friedberg, Boris Sepesi, Julie S. Deutsch, Tricia Cottrell, Janis Taube, Peter B. Illei, Kellie N. Smith, Drew M. Pardoll, Anne S. Tsao, Julie R. Brahmer, Valsamo Anagnostou, Patrick M. Forde","doi":"10.1038/s41591-025-03958-3","DOIUrl":"https://doi.org/10.1038/s41591-025-03958-3","url":null,"abstract":"<p>Immune checkpoint blockade (ICB) is standard of care in advanced diffuse pleural mesothelioma (DPM), but its role in the perioperative management of DPM is unclear. In tandem, circulating tumor DNA (ctDNA) ultra-sensitive residual disease detection has shown promise in providing a molecular readout of ICB efficacy across resectable cancers. This phase 2 trial investigated neoadjuvant nivolumab and nivolumab/ipilimumab in resectable DPM along with tumor-informed liquid biopsy residual disease assessments. Patients with resectable epithelioid/biphasic DPM enrolled sequentially to nivolumab 240 mg every 2 weeks (q2w) for three cycles (Arm A, <i>n</i> = 16) or nivolumab 3 mg kg⁻¹ q2w for three cycles plus ipilimumab 1 mg kg⁻¹ on cycle 1 (Arm B, <i>n</i> = 14), followed by surgery, optional chemotherapy and/or radiotherapy, and nivolumab 480 mg q4w for 1 year. Co-primary endpoints included safety and feasibility; key exploratory endpoints included progression-free survival (PFS), overall survival (OS) and ctDNA analyses. The trial met its primary endpoints, and, in Arms A and B, 81.3% and 85.7% of patients proceeded to surgery, respectively. Treatment was safe, with a single dose-limiting toxicity in each arm. In Arm A, median PFS and OS were 9.6 months (95% confidence interval (CI): 2.5–27.7) and 19.3 months (95% CI: 14.9–34.7), respectively. In Arm B, median PFS and OS were 19.8 months (7.1–not reached) and 28.6 months (20.4–not reached), respectively. Persistent ctDNA was detected during neoadjuvant therapy in patients who did not undergo complete surgical resection due to disease progression (Fisher’s exact test, <i>P</i> = 0.00013). Patients with detectable ctDNA on cycle 3 and pre-surgery had shorter PFS (log-rank test, <i>P</i> = 0.027 and <i>P</i> = 0.0059, respectively); this association was more pronounced when quantitative ctDNA changes were considered (log-rank test, <i>P</i> = 1.8 × 10⁻⁶). Our findings support the feasibility of neoadjuvant ICB and the clinical utility of ctDNA analyses to capture residual disease in resectable DPM. ClinicalTrials.gov identifier: NCT03918252.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"51 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008946","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":"Heterologous two-dose Ebola vaccine regimen in pregnant women in Rwanda: a randomized controlled phase 3 trial","authors":"Julien Nyombayire, Rosine Ingabire, Amelia Mazzei, Tyronza Sharkey, Claudine Umuhoza, Jeannine Mukamuyango, Susan Allen, Amanda Tichacek, Rachel Parker, Kristin M. Wall, Michael Katwere, Babajide Keshinro, Auguste Gaddah, Yan Wang, Chiara A. Forcheh, Chelsea McLean, Valérie Oriol-Mathieu, Kerstin Luhn, Cynthia Robinson, Etienne Karita","doi":"10.1038/s41591-025-03932-z","DOIUrl":"https://doi.org/10.1038/s41591-025-03932-z","url":null,"abstract":"<p>Risk of death for both mother and fetus following Ebola virus infection is extremely high. In this study, healthy women in Rwanda aged ≥18 years were randomized to two-dose Ebola vaccination (Ad26.ZEBOV, MVA-BN-Filo) during pregnancy (group A) or postpartum (group B). Unvaccinated pregnant group B women served as control. This was a parallel, randomized, controlled, open-label, single-center trial to evaluate the safety (primary endpoint—outcomes of interest and serious adverse events (SAEs)) and immunogenicity (secondary endpoint) of the two-dose Ebola vaccination. Among 3,484 women screened, 2,013 were randomized, and 2,012 women and 1,945 infants born alive were descriptively analyzed. Adverse outcomes of interest occurred in women (5.2% in group A and 7.3% in group B) and infants (26.0% in group A and 25.6% in group B). The most common maternal outcome of interest was pathways to preterm birth (3.2% in group A and 3.4% in group B), and the most common infant outcome of interest was small for gestational age (14.3% in group A and 11.8% in group B). Maternal/fetal and neonatal/infant SAE frequencies were comparable between groups (9.8% in group A, 9.0% in group B and 21.9% in group A, 15.9% in group B, respectively). Anti-Ebola virus glycoprotein-specific binding antibody response (secondary endpoint) was sustained in ≥90% of women at 1 year postdose 1. In group A, binding antibodies were detected in cord blood (99%) and infant serum (95%) samples 14 weeks postbirth. The trial met all primary and secondary objectives. Ad26.ZEBOV, MVA-BN-Filo did not raise concerns regarding adverse maternal/fetal or neonatal/infant outcomes, had no unexpected safety issues, and induced binding antibody responses in women and offspring through passive transfer. ClinicalTrials.gov registration: NCT04556526.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"41 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009044","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":"Publisher Correction: GD2-targeting CAR T cells in high-risk neuroblastoma: a phase 1/2 trial","authors":"Franco Locatelli, Daria Pagliara, Maria A. De Ioris, Marco Becilli, Giada Del Baldo, Annalisa Serra, Angela Mastronuzzi, Maria G. Cefalo, Giuseppina Li Pira, Giovanna Leone, Valentina Bertaina, Francesco Fabozzi, Matteo Di Nardo, Chiara Rosignoli, Maria Luisa D’Andrea, Alessandro Crocoli, Sabina Vennarini, Matilde Sinibaldi, Stefano Di Cecca, Marika Guercio, Laura Iaffaldano, Barbarella Lucarelli, Mattia Algeri, Pietro Merli, Giovanna S. Colafati, Biagio De Angelis, Concetta Quintarelli, Francesca del Bufalo","doi":"10.1038/s41591-025-03996-x","DOIUrl":"https://doi.org/10.1038/s41591-025-03996-x","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-025-03874-6, published online 21 August 2025.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"163 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017827","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":"Building the world’s first truly global medical foundation model","authors":"Yih Chung Tham, Jocelyn Hui Lin Goh, Paul Nderitu, Yukun Zhou, An Ran Ran, Sahana Srinivasan, Gabriel Dawei Yang, Gatera Fiston Kitema, Polly Rawlinson, Hongyang Jiang, Ke Zou, Carol Y. Cheung, Pearse A. Keane","doi":"10.1038/s41591-025-03859-5","DOIUrl":"https://doi.org/10.1038/s41591-025-03859-5","url":null,"abstract":"<p>Since 2022, the field of medical artificial intelligence (AI) has begun a shift toward foundation models, machine learning systems that are trained on broad data at scale and are adaptable to a wide range of downstream tasks^1,2. Medical foundation models are rapidly evolving, driven by the synergy of expanding medical data repositories, advances in neural network architecture (especially transformers), self-supervised learning approaches and computing power. Medical foundation models are capable of performing, or can be adapted to perform, a range of medical tasks with a minimal amount of annotated data. To date, several promising breakthroughs with foundation models have been demonstrated across diverse medical domains, including pathology, radiology and ophthalmology^3,4,5.</p><p>Nevertheless, training robust medical foundation models requires large, diverse and clinically useful representative data⁶. Assembling such datasets remains a major challenge for the research community because of strict data-sharing regulations intended to protect patient privacy and ensure ethical compliance. For these reasons, most existing foundational models are trained on datasets that are geographically and demographically ‘narrow’ (that is, not globally representative), limiting their generalizability and effectiveness, particularly in under-represented regions and populations^6,7,8.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"52 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009043","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":"Tirzepatide drives weight loss in people with obesity due to MC4R deficiency","authors":"","doi":"10.1038/s41591-025-03915-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03915-0","url":null,"abstract":"We studied people with obesity involved in the SURMOUNT-1 trial of the dual GLP-1 and GIP receptor agonist, tirzepatide. People with pathogenic variants of the gene encoding the melanocortin 4 receptor (MC4R) lost a similar amount of weight to people with an intact gene, demonstrating that tirzepatide is effective in MC4R deficiency.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"15 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995646","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":"Pridopidine in early-stage manifest Huntington’s disease: a phase 3 trial","authors":"Ralf Reilmann, Andrew Feigin, Anne E. Rosser, Sandra K. Kostyk, Carsten Saft, Yael Cohen, Henk Schuring, Randal Hand, Andrew M. Tan, Kelly Chen, Wei Feng, Leehee Navon-Perry, Andres Cruz-Herranz, Christine Syltevik, Diderik Boot, Ferdinando Squitieri, Elise Kayson, Munish Mehra, Y. Paul Goldberg, Michal Geva, Michael R. Hayden","doi":"10.1038/s41591-025-03920-3","DOIUrl":"https://doi.org/10.1038/s41591-025-03920-3","url":null,"abstract":"<p>Huntington’s disease (HD) is a rare, neurodegenerative disorder for which only symptomatic treatments are available. The PROOF-HD study was a randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of pridopidine, a selective Sigma-1 receptor agonist, in HD. The primary and key secondary endpoints, change in total functional capacity (TFC) and composite Unified Huntington’s Disease Rating Scale (cUHDRS) score at week 65, were not met in the overall population. The TFC least-squares mean difference between pridopidine and placebo was −0.18 (95% confidence interval −0.49 to 0.14; <i>P</i> = 0.26). The cUHDRS least-squares mean difference between pridopidine and placebo was −0.11 (95% confidence interval −0.40 to 0.18; <i>P</i> = 0.45). Sensitivity analysis in a subgroup of participants not treated with antidopaminergic medications at any time demonstrated a consistent pattern favoring pridopidine across multiple measures, including TFC and cUHDRS. Notably, pridopidine 45 mg twice daily demonstrated a favorable safety and tolerability profile. Taken together, pridopidine has the potential to address a critical unmet need in HD. ClinicalTrials.gov identifier: NCT04556656.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"62 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995648","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":"Echocardiography gets to the heart of cardiac amyloidosis","authors":"Diana Bonderman","doi":"10.1038/s41591-025-03940-z","DOIUrl":"https://doi.org/10.1038/s41591-025-03940-z","url":null,"abstract":"Imaging data support the clinical effects of RNA interference agent vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy — and point to a potential new role for echocardiographic parameters in monitoring individual treatment responses.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"71 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995645","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}