Med最新文献

{"title":"Multidisciplinary expert consensus on diagnosis and treatment of multiple lung cancers.","authors":"Kezhong Chen, Anwen Liu, Changli Wang, Chengping Hu, Chun Chen, Fan Yang, Haiquan Chen, Hongbing Shen, Hongtao Zhang, Hongxu Liu, Jianping Xiong, Jie Wang, Li Zhang, Lin Xu, Lvhua Wang, Mingfang Zhao, Qiang Li, Qibin Song, Qinghua Zhou, Qun Wang, Shenglin Ma, Shidong Xu, Shuanghu Yuan, Shugeng Gao, Shun Lu, Weimin Li, Weimin Mao, Xiaoqing Liu, Xiaorong Dong, Xuening Yang, Yilong Wu, Ying Cheng, Yong Song, Yunchao Huang, Zhenfa Zhang, Zhiwei Chen, Zhiyong Ma, Christoph C Zielinski, Yu Shyr, Jun Wang","doi":"10.1016/j.medj.2025.100643","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100643","url":null,"abstract":"<p><p>The rising incidence of multiple lung cancers (MLCs), encompassing multiple primary lung cancers (MPLCs) and intrapulmonary metastasis (IPM), poses two significant clinical challenges. First, distinguishing between MPLC and IPM remains difficult due to insufficiently accurate criteria and ambiguous integration of genetic testing. Second, standardized therapeutic protocols are still lacking. To address these issues, the Lung Cancer Expert Committee of China Anti-Cancer Association (CACA) assembled a multidisciplinary expert panel spanning thoracic surgery, pulmonary medicine, oncology, radiology, and pathology. Following a comprehensive literature review ending on October 23, 2024, the panel engaged in iterative discussions and conducted two rounds of expert voting, culminating in 25 evidence-based recommendations across five key domains: epidemiology, pre-treatment evaluation, definitive diagnostics, surgical treatment, and non-surgical treatment. This consensus provides clinicians with practical guidance to enhance diagnostic precision and therapeutic decision-making in MLC management while highlighting unmet needs to inform future guideline development.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100643"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040065","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}

{"title":"Multi-year enzyme expression in patients with mucopolysaccharidosis type VI after liver-directed gene therapy.","authors":"Alessandro Rossi, Roberta Romano, Simona Fecarotta, Margherita Dell'Anno, Valentina Pecorella, Roberta Passeggio, Stefano Zancan, Giancarlo Parenti, Francesca Santamaria, Francesco Borgia, Federica Deodato, Silvia Funghini, Charles A Rupar, Chitra Prasad, Mar O'Callaghan, John J Mitchell, Maria Grazia Valsecchi, Giancarlo la Marca, Stefania Galimberti, Alberto Auricchio, Nicola Brunetti-Pierri","doi":"10.1016/j.medj.2024.10.021","DOIUrl":"10.1016/j.medj.2024.10.021","url":null,"abstract":"<p><strong>Background: </strong>Mucopolysaccharidosis type VI (MPS VI) is due to a deficiency of the lysosomal enzyme arylsulfatase B (ARSB) that results in multi-organ accumulation of glycosaminoglycans (GAGs). Limitations of current treatments prompted the development of a liver-directed gene therapy clinical trial for MPS VI.</p><p><strong>Methods: </strong>We report the long-term follow-up of patients with MPS VI who discontinued enzyme replacement therapy (ERT) and received a single intravenous infusion of high-dose (6 × 10¹² genome copies/kg) recombinant adeno-associated virus serotype 8 (AAV8) vector expressing ARSB under the control of a liver-specific promoter (ClinicalTrials.gov: NCT03173521). Primary outcomes were safety and urinary GAG excretion. Secondary outcomes were endurance and respiratory function.</p><p><strong>Findings: </strong>Median follow-up time was 45 months (n = 4, three females and one male; age range: 5-10 years). No late-emergent safety events were observed. Patients showed sustained serum ARSB activity (38%-67% of mean healthy reference values), a modest increase in urinary GAG concentrations, and no relevant changes in endurance, cardiac, or pulmonary function. In one of the four patients, ERT was restarted because of elevated urinary GAGs without decreased serum ARSB activity up to about 2.5 years after gene transfer. Liver and spleen size remained within the reference ranges.</p><p><strong>Conclusions: </strong>A single intravenous administration of AAV8.TBG.hARSB was safe and resulted in sustained ARSB expression and a modest increase in urinary GAGs in most patients, thus supporting liver-directed gene therapy for MPS VI.</p><p><strong>Funding: </strong>This study was sponsored by the Telethon Foundation ETS, the European Union, the Isaac Foundation, and the Italian Ministry of University and Research.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100544"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639949","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}

{"title":"A genetic fingerprint associated with durable HIV remission after interruption of antiretroviral treatment: ANRS VISCONTI/PRIMO.","authors":"Asma Essat, Anaïs Chapel, Kahina Amokrane, Valérie Monceaux, Céline Didier, Adeline Melard, Elise Gardiennet, Véronique Avettand-Fenoel, Sylvie Orr, Faroudy Boufassa, Olivier Lambotte, Michaela Müller-Trutwin, Camille Lécuroux, Antoine Chéret, Cécile Goujard, Christine Rouzioux, Sophie Caillat-Zucman, Laurent Hocqueloux, Daniel Scott-Algara, Laurence Meyer, Asier Sáez-Cirión","doi":"10.1016/j.medj.2025.100670","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100670","url":null,"abstract":"<p><strong>Background: </strong>There is currently no curative treatment for HIV-1 infection. However, some individuals (defined as posttreatment controllers) durably control viremia after the discontinuation of antiretroviral therapy (ART). Although the ability to achieve this HIV-1 remission status is enhanced by early treatment initiation, the mechanisms leading to posttreatment HIV-1 control remain unclear.</p><p><strong>Methods: </strong>We retrospectively explored the immunogenetic characteristics of long-term posttreatment controllers from the ANRS VISCONTI study and persons monitored since primary HIV-1 infection in the ANRS PRIMO cohort and evaluated their influence on clinical parameters and outcome after ART discontinuation.</p><p><strong>Findings: </strong>We identified a major histocompatibility complex (MHC)-related fingerprint favoring sustained HIV-1 remission. HLA-B∗35 alleles, which are associated with rapid progression to AIDS during natural HIV-1 infection, were paradoxically overrepresented among posttreatment controllers and had a positive impact on outcome after treatment discontinuation in people who began therapy during primary infection. Specifically, the influence of HLA-B∗35 alleles was observed when they were carried in combination with other HLA class I alleles expressing Bw4 and C2 ligands of killer immunoglobulin-like receptors (KIRs) in a genetic context that favors KIR education of natural killer (NK) cells (Bw4TTC2 genotype). Accordingly, posttreatment controllers with HLA-B∗35 alleles carry distinct KIR genotypes and NK cells.</p><p><strong>Conclusions: </strong>The combination of HLA-B∗35 with Bw4TTC2 genotype, associated with KIR education of NK cells, was abundant among posttreatment HIV-1 controllers and promoted viral control after interruption of early-initiated antiretroviral treatment. These results support a role of NK cells in sustained HIV-1 remission.</p><p><strong>Funding: </strong>The VISCONTI study and the PRIMO cohort are funded by the ANRS-MIE.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100670"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018906","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}

{"title":"CD70-targeted cancer theranostics: Progress and challenges.","authors":"Weijun Wei, Viktor Grünwald, Ken Herrmann","doi":"10.1016/j.medj.2025.100671","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100671","url":null,"abstract":"<p><p>CD70, a tumor-associated antigen, exhibits elevated expression in clear cell renal cell carcinoma (ccRCC), nasopharyngeal carcinoma, and lymphoma, among others, with minimal presence in healthy tissues. CD70 has emerged as a promising biomarker for molecular imaging, targeted therapies, and immunotherapies. ImmunoPET imaging with single-domain antibody-derived tracers, such as [¹⁸F]RCCB6 and [⁶⁸Ga]Ga-NOTA-RCCB6, demonstrates exceptional diagnostic precision, identifying both common and rare metastases from ccRCC. This capability enhances staging accuracy and further enables early intervention. Beyond diagnostics, CD70-targeted imaging optimizes patient selection for emerging therapies, such as CAR-T cells and antibody-drug conjugates, by stratifying candidates based on their CD70 expression levels. It also supports real-time monitoring of therapeutic responses, enabling dynamic adjustments to treatment. The integration of these imaging tools into clinical workflows enhances personalized treatment efficacy for CD70-expressing cancers. Radiotheranostic strategies can further allow the simultaneous diagnosis and treatment of malignancies, opening new horizons for the precise management of CD70⁺ tumors.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100671"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052658","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}

{"title":"Diagnosing recipient- vs. donor-derived posttransplant myelodysplastic neoplasm via targeted single-cell mutational profiling.","authors":"Jana Ihlow, Livius Penter, Lam Giang Vuong, Philip Bischoff, Benedikt Obermayer, Alexandra Trinks, Olga Blau, Anke Behnke, Thomas Conrad, Markus Morkel, Catherine J Wu, Jörg Westermann, Lars Bullinger, Ann-Christin von Brünneck, Nils Blüthgen, David Horst, Samantha D Praktiknjo","doi":"10.1016/j.medj.2024.11.001","DOIUrl":"10.1016/j.medj.2024.11.001","url":null,"abstract":"<p><strong>Background: </strong>Distinguishing donor- vs. recipient-derived myelodysplastic neoplasm (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is challenging and has direct therapeutical implications.</p><p><strong>Methods: </strong>Here, we took a translational approach that we used in addition to conventional diagnostic techniques to resolve the origin of MDS in a 38-year-old patient with acquired aplastic anemia and evolving MDS after first allo-HSCT. Specifically, we used single-cell transcriptional profiling to differentiate between donor- and recipient-derived bone marrow cells and established a strategy that additionally allows identification of cells carrying the MDS-associated U2AF1^S34Y variant.</p><p><strong>Results: </strong>The patient exhibited mixed donor chimerism combined with severely reduced erythropoiesis and dysplastic morphology within the granulocytic and megakaryocytic lineage along with the MDS-associated U2AF1^S34Y mutation in the bone marrow. Single-cell transcriptional profiling together with targeted enrichment of the U2AF1^S34Y-specific locus further revealed that, while the immune compartment was mainly populated by donor-derived cells, myelopoiesis was predominantly driven by the recipient. Additionally, concordant with recipient-derived MDS, we found that U2AF1^S34Y-mutated cells were exclusively recipient derived with X but not Y chromosome-specific gene expression.</p><p><strong>Conclusion: </strong>Our study highlights the clinical potential of integrating high-resolution single-cell techniques to resolve complex cases for personalized treatment decisions.</p><p><strong>Funding: </strong>The study was funded by intramural resources of the Charité - Universitätsmedizin Berlin and the Berlin Institute of Health.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100548"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792447","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}

{"title":"BilT03: Phase 1b/2 multicenter trial of nivolumab with 5-fluorouracil and liposomal irinotecan for previously treated advanced biliary tract cancer.","authors":"Vaibhav Sahai, Kent A Griffith, Bruce S Lin, Heloisa P Soares, Sreenivasa R Chandana, Oxana Crysler, Chandan Kumar-Sinha, Thomas Enzler, Dominique Dippman, Valerie Gunchick, Mark M Zalupski","doi":"10.1016/j.medj.2024.10.024","DOIUrl":"10.1016/j.medj.2024.10.024","url":null,"abstract":"<p><strong>Background: </strong>Second-line chemotherapy with 5-fluorouracil/leucovorin (5FULV) and liposomal irinotecan improves survival in advanced biliary tract cancer (BTC). In this phase 1b/2 trial, we investigated the combination of 5FULV and liposomal irinotecan with nivolumab following progression on first-line chemotherapy for advanced BTC.</p><p><strong>Methods: </strong>Patients received 2,400 mg/m² 5-fluorouracil, leucovorin (dose level: 0:400 or -1:200 mg/m²), 70 mg/m² liposomal irinotecan, and 240 mg nivolumab every 2 weeks (ClinicalTrials.gov: NCT03785873). The phase 1b and 2 primary objectives included recommended phase 2 dose (RP2D) and median progression-free survival (PFS; null and alternative hypotheses of 2.9 and 5.0 months) with a two-sided alpha of 0.05 and >80% power. Secondary objectives were safety, objective response rate (ORR), and overall survival (OS).</p><p><strong>Findings: </strong>Of 30 patients with a median age of 63.5 years, 18 (60%) were men, 25 (83%) were White, 16 (53%) had an ECOG performance status of 0, and 19 (63.3%) had intrahepatic cholangiocarcinoma. In phase 1b, the RP2D was dose level 0 after a dose-limiting toxicity event of enterocolitis (n = 1). Median PFS was 4.1 months (95% confidence interval [CI], 1.9-9.9). The ORR was 16.7% (5 partial responses) per irRECIST, the median OS was 7.4 months (95% CI, 5.7-15.9), and the 24-month survival rate was 23.3%. The most common grade ≥3 treatment-related adverse events were diarrhea (5; 16.7%), fatigue (4; 13.3%), and neutropenia (3; 10%).</p><p><strong>Conclusions: </strong>Treatment was well tolerated, but the primary endpoint was not met. The median OS was similar to prior trials with this drug combination, but the 24-month survival rate was higher than expected.</p><p><strong>Funding: </strong>This work was funded by Ipsen Biopharmaceuticals, Bristol-Myers Squibb (CA209-8LF), and the University of Michigan Rogel Cancer Center (P30CA046592).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100547"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865599","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}

{"title":"Body ownership alterations in stroke emerge from reduced proprioceptive precision and damage to the frontoparietal network.","authors":"Giulio Mastria, Tommaso Bertoni, Henri Perrin, Nikita Akulenko, Gaia Risso, Michel Akselrod, Eleonora Guanziroli, Franco Molteni, Patric Hagmann, Michela Bassolino, Andrea Serino","doi":"10.1016/j.medj.2024.10.013","DOIUrl":"10.1016/j.medj.2024.10.013","url":null,"abstract":"<p><strong>Background: </strong>Stroke patients often experience alterations in their subjective feeling of ownership for the affected limb, which can hinder motor function and interfere with rehabilitation. In this study, we aimed at disentangling the complex relationship between sensory impairment, body ownership (BO), and motor control in stroke patients.</p><p><strong>Methods: </strong>We recruited 20 stroke patients with unilateral upper limb sensory deficits and 35 age-matched controls. Participants performed a virtual reality reaching task with a varying displacement between their real unseen hand and a visible virtual hand. We measured reaching errors and subjective ownership ratings as indicators of hand ownership. Reaching errors were modeled using a probabilistic causal inference model, in which ownership for the virtual hand is inferred from the level of congruency between visual and proprioceptive inputs and used to weigh the amount of visual adjustment to reaching movements.</p><p><strong>Findings: </strong>Stroke patients were more likely to experience ownership over an incongruent virtual hand and integrate it into their motor plans. The model explained this tendency in terms of a decreased capability of detecting visuo-proprioceptive incongruences, proportionally to the amount of proprioceptive deficit. Lesion analysis further revealed that BO alterations, not fully explained by the proprioceptive deficit, are linked to frontoparietal network damage, suggesting a disruption in higher-level multisensory integration functions.</p><p><strong>Conclusions: </strong>Collectively, our results show that BO alterations in stroke patients can be quantitatively predicted and explained in a computational framework as the result of sensory loss and higher-level multisensory integration deficits.</p><p><strong>Funding: </strong>Swiss National Science Foundation (163951).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100536"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629099","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}

{"title":"GLP-1 agonists to slow down Parkinson's progression? The quest continues.","authors":"Bastiaan R Bloem, Eric A Macklin, Michael A Schwarzschild","doi":"10.1016/j.medj.2025.100645","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100645","url":null,"abstract":"<p><p>A much-anticipated phase 3 clinical trial (EXENATIDE-PD3) tested whether exenatide, a GLP-1 receptor agonist used to treat type 2 diabetes, might be neuroprotective in persons with Parkinson's disease.¹ There was no difference between exenatide and matched placebo for the primary outcome or any secondary or exploratory outcomes. We discuss the implications for future attempts to modify the course of Parkinson's disease.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100645"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022291","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}

{"title":"A cluster randomized trial of xylitol chewing gum for prevention of preterm birth: The PPaX trial.","authors":"Gregory C Valentine, Kathleen M Antony, Haleh Sangi-Haghpeykar, Alexis C Wood, Rose Chirwa, Saukani Petro, Mary Dumba, Deborah Nanthuru, Cynthia Shope, Jesse Mlotha-Namarika, Jeffrey Wilkinson, Joshua Aagaard, Ellen J Aagaard, Maxim D Seferovic, Judy Levison, Peter Kazembe, Kjersti M Aagaard","doi":"10.1016/j.medj.2024.10.016","DOIUrl":"10.1016/j.medj.2024.10.016","url":null,"abstract":"<p><strong>Background: </strong>Maternal periodontal disease is associated with preterm and low-birthweight deliveries, but randomized trials of likely efficacious treatments (e.g., dental scaling and root planing) during pregnancy have not reduced these adverse outcomes. As an alternative, we hypothesized that periconception initiation of xylitol chewing gum would reduce the occurrence of preterm or low-birthweight deliveries among a historical high-prevalence population in Malawi.</p><p><strong>Methods: </strong>We conducted an open-label, parallel-enrollment, matched-pair, cluster-randomized, controlled clinical trial across eight health centers (sites) in and around Lilongwe, Malawi. Sites were paired by anticipated delivery volume and randomized to prenatal and oral health education alone (active control) or with twice-daily xylitol chewing gum (intervention) throughout the periconception and antenatal periods. For the primary prevention of preterm (<37 weeks) and low-birthweight (<2,500 g) deliveries (co-primary outcomes), comparison by allocation group was performed using generalized linear mixed models for each outcome as a fixed factor and the site(s) as a random factor.</p><p><strong>Findings: </strong>10,069 participants were enrolled (n = 4,549 at intervention sites, n = 5,520 at active control sites), with >95% available for analyses. Initiation of xylitol chewing gum resulted in significant reductions in the co-primary outcomes: preterm birth (12.6% [549/4,349] vs. 16.5% [878/5,321]; relative risk [RR] 0.76, 95% confidence interval [CI] 0.57-0.99) and <2,500-g neonates (8.9% [385/4,305] vs. 12.9% [679/5,260]; RR 0.70, 95% CI 0.49-0.99). Xylitol chewing gum use also led to fewer neonatal demises (0.2% [8/4,305] vs. 0.4% [22/5,260]; RR 0.41, 95% CI 0.19-0.89).</p><p><strong>Conclusions: </strong>Periconception initiation and ongoing use of xylitol chewing gum significantly reduced the occurrence of preterm and low-birthweight deliveries in Malawi.</p><p><strong>Funding: </strong>E.W. Al Thrasher Foundation (to K.A.) and USAID Saving Lives at Birth Grand Challenges Grant AID-OAA-G-11-00062 (to K.A.). Additional financial and in-kind support was graciously provided by Texas Children's Hospital and Baylor Foundation Malawi.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100539"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629076","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}

{"title":"Organoids and organs-on-chips: Recent advances, applications in drug development, and regulatory challenges.","authors":"Liangbin Zhou, Jingjing Huang, Cun Li, Qi Gu, Gang Li, Zhong Alan Li, Jiankun Xu, Jie Zhou, Rocky S Tuan","doi":"10.1016/j.medj.2025.100667","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100667","url":null,"abstract":"<p><p>Organoids and organs-on-chips (OoCs) are rapidly evolving technologies for creating miniature human tissue models. They can mimic complex physiological functions and pathological conditions, offering more realistic platforms for disease modeling, drug screening, precision medicine, and regenerative therapies. The passing of the FDA Modernization Act 2.0 has reduced animal testing requirements for drug trials, marking a significant milestone in using advanced in vitro models such as organoids and OoCs for therapeutic discovery. Apart from technical and ethical challenges, regulatory issues persist in ensuring the reliability, scientificity, and applicability of these models in drug development. This perspective explores the concept, advancements, pros and cons, and applications of organoids and OoCs, particularly in drug research and development. It also examines global regulatory agencies' policies and actions on using these models in drug evaluation, aiming to guide industry standard setting and advance regulatory science.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100667"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045540","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}