Med最新文献

{"title":"Genomic landscape and molecularly informed therapy in thymic carcinoma and other advanced thymic epithelial tumors.","authors":"Lino Möhrmann, Lysann Rostock, Maximilian Werner, Małgorzata Oleś, Jonas S Arnold, Nagarajan Paramasivam, Korinna Jöhrens, Luise Rupp, Marc Schmitz, Daniela Richter, Sebastian Uhrig, Martina Fröhlich, Barbara Hutter, Jennifer Hüllein, Arne Jahn, Marie Arlt, Elena E Möhrmann, Dorothea Hanf, Laura Gieldon, Simon Kreutzfeldt, Christoph E Heilig, Maria-Veronica Teleanu, Daniel B Lipka, Katja Beck, Annika Baude-Müller, Andreas Mock, Ivan Jelas, Damian T Rieke, Marcel Wiesweg, Christian Brandts, Melanie Boerries, Anna L Illert, Alexander Desuki, Thomas Kindler, Angela M Krackhardt, C Benedikt Westphalen, Petros Christopoulos, Leonidas Apostolidis, Albrecht Stenzinger, Michael Allgäuer, Olaf Neumann, Irina A Kerle, Peter Horak, Christoph Heining, Heidrun Grosch, Evelin Schröck, Daniel Hübschmann, Stefan Fröhling, Hanno Glimm","doi":"10.1016/j.medj.2025.100612","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100612","url":null,"abstract":"<p><strong>Background: </strong>Thymic epithelial tumors (TETs) are rare malignancies with limited treatment options and underexplored molecular features.</p><p><strong>Methods: </strong>We examined the genomic landscape and therapeutic outcomes in 81 patients with advanced TETs, including thymic carcinomas (TCs), thymomas, and thymic neuroendocrine neoplasms (TNENs), who were enrolled in the MASTER trial, a prospective observational precision oncology trial.</p><p><strong>Findings: </strong>Using whole-genome-sequencing and whole-exome-sequencing analysis, transcriptome analysis, and methylome analysis, we identified distinct molecular features across TET subtypes, including a higher tumor mutational burden in TC and pathogenic germline variants in 18% of cases. We performed transcriptome- and methylome-based unsupervised clustering and were able to divide TCs into immunologically hot and cold subsets, with hot TCs exhibiting higher T cell infiltration and significantly longer overall survival. In 65 out of 76 (86%) patients, we recommended molecularly informed therapies, which were applied in 29 out of 65 (45%) cases, leading to a disease control rate of 62% and an objective response rate of 23% (both n = 26). The progression-free survival ratio (PFSr) was > 1.3 in 8 out of 24 (33%) patients, 7 of them having TC. Among TCs, patients achieved a mean PFSr of 1.4, indicating potential therapeutic advantages in this subgroup. The PFSr between the PFS of immune checkpoint inhibition and preceding therapies was significantly higher in the hot cluster compared to the cold cluster (median 1.7 vs. 0.3; p = 0.01945).</p><p><strong>Conclusions: </strong>Our findings expand the understanding of TET biology and emphasize the role of precision oncology in informing treatment decisions and improving outcomes for patients with advanced TETs, particularly in TCs.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100612"},"PeriodicalIF":12.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664606","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":"Global, multi-center, repeat-dose, phase 2 study of RZ358 (ersodetug), an insulin receptor antibody, for congenital hyperinsulinism.","authors":"Huseyin Demirbilek, Maria Melikyan, Violeta Iotova, Sonya Galcheva, Mehmet Nuri Ozbek, Antonia Dastamani, Nino Kheladze, Kineret Mazor-Aronovitch, Maria Clemente, Susann Empting, Klaus Mohnike, Henrik Thybo Christesen, Paul S Thornton, Diva D De Leon, Davelyn Hood, Erin O'Boyle, Brian K Roberts","doi":"10.1016/j.medj.2025.100611","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100611","url":null,"abstract":"<p><strong>Background: </strong>Congenital hyperinsulinism (cHI) is a rare, primarily pediatric disease characterized by dysregulated insulin secretion resulting in severe, persistent hypoglycemia, frequently leading to lifelong neurologic impairments. The safety, pharmacokinetics, and glycemic efficacy of ersodetug, a fully human monoclonal antibody that allosterically and reversibly binds the insulin receptor (INSR) and reduces excess insulin action, are being evaluated for the treatment of cHI-related hypoglycemia.</p><p><strong>Methods: </strong>A global, open-label, phase 2b study (ClinicalTrials.gov: NCT04538989) was conducted in 23 patients with cHI with persistent hypoglycemia on standard-of-care (SOC) therapies. Eligible participants (age ≥2 years) received add-on ersodetug at dose levels between 3 and 9 mg/kg intravenously (i.v.) bi-weekly for 8 weeks in 4 sequential dose cohorts.</p><p><strong>Findings: </strong>Enrolled participants (average age = 6.7 years) on SOC (87% medications; 17% previous pancreatectomy) experienced 13 events/week and 23% time in hypoglycemia at baseline. Ersodetug resulted in predictable, dose-proportional pharmacokinetics. No deaths, adverse drug reactions, study withdrawals, or dose-limiting toxicities occurred. Hypoglycemia (<70 mg/dL) events (self-monitored blood glucose) and time (continuous glucose monitoring) improved from baseline by medians of 59% (p < 0.001) and 54% (p < 0.001), respectively, across pooled dose levels and by 48%-84% (events) and 61%-65% (time) at doses of 6 or 9 mg/kg (p < 0.05) with a nearly universal individual patient response rate. Additional hypoglycemia metrics, including overnight hypoglycemia, similarly improved.</p><p><strong>Conclusion: </strong>Ersodetug was generally well tolerated and significantly improved hypoglycemia in participants with cHI. Ersodetug represents a novel INSR-targeted mechanism of action with the potential to be an effective therapy for all forms of cHI, alone or in combination with other therapies.</p><p><strong>Funding: </strong>Rezolute, Inc. (Redwood City, CA), provided funds.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100611"},"PeriodicalIF":12.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664610","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":"Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome.","authors":"Alan K Percy, Robin Ryther, Eric D Marsh, Jeffrey L Neul, Timothy A Benke, Elizabeth M Berry-Kravis, Timothy Feyma, David N Lieberman, Amitha L Ananth, Cary Fu, Colleen Buhrfiend, Amy Barrett, Dilesh Doshi, Mona Darwish, Di An, Kathie M Bishop, James M Youakim","doi":"10.1016/j.medj.2025.100608","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100608","url":null,"abstract":"<p><strong>Background: </strong>Trofinetide is the first available treatment for Rett syndrome (RTT) and is approved in the United States in adults and pediatric patients aged ≥2 years. The DAFFODIL study was conducted in girls aged 2-4 years with RTT to examine the safety, tolerability, and efficacy of trofinetide and to validate that the recommended dosage, according to body weight, achieved target exposure.</p><p><strong>Methods: </strong>DAFFODIL was a phase 2/3, open-label study of trofinetide consisting of two treatment periods (12 weeks [period A] and ∼21 months [period B]). Pharmacokinetic samples were collected at regular intervals during period A. Assessments included treatment-emergent adverse events (TEAEs) and exploratory efficacy (Clinical Global Impressions-Improvement [CGI-I], CGI-Severity, caregiver GI-I [CaGI-I], and overall quality of life rating of the Impact of Childhood Neurologic Disability Scale [ICND-QoL]). Optional caregiver exit interviews were also conducted.</p><p><strong>Findings: </strong>Fifteen participants were enrolled. Overall, the most common TEAEs were diarrhea (80.0%) and vomiting (53.3%), which were mild or moderate in severity. Steady-state exposure at clinical doses fell within the target exposure range. RTT symptoms improved throughout the study as measured by the CGI-I, CaGI-I, and change from baseline in the ICND-QoL. In caregiver interviews (n = 7), all caregivers reported they were \"very satisfied\" or \"satisfied\" with trofinetide benefits.</p><p><strong>Conclusions: </strong>Trofinetide has acceptable tolerability in girls 2-4 years of age with RTT and provides long-term efficacy. Weight-based dosage achieves target exposure in younger children.</p><p><strong>Funding: </strong>The study was supported by Acadia Pharmaceuticals (San Diego, CA). This study was registered at ClinicalTrials.gov (NCT04988867).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100608"},"PeriodicalIF":12.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568455","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 progranulin variant causing childhood interstitial lung disease responsive to anti-TNF-α biologic therapy.","authors":"John C Kennedy, Sara O Vargas, Martha P Fishman, Nicola Alesi, Seung-Han Baek, Damir Khabibillin, Craig D Platt, Carolina Garcia-de-Alba, Pankaj B Agrawal, Nikkola E Carmichael, Lauren A Henderson, Andrew Wehrman, Sebastian Boland, Tobias Walther, Robert V Farese, Alicia M H Casey, John P Manis, Lauren V Collen, Maria Lvova, Alessandro Barbieri, Brendan Sullivan, Benjamin A Raby","doi":"10.1016/j.medj.2025.100607","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100607","url":null,"abstract":"<p><strong>Background: </strong>Childhood interstitial and diffuse lung diseases are a collection of rare disorders with significant associated morbidity. Only a small subset of these diseases have precise diagnostic or therapeutic options identified to date.</p><p><strong>Methods: </strong>Whole-exome sequencing in a family identified a candidate pathogenic variant predicted to be causing fibrotic lung and liver disease in a child. Digital spatial mRNA profiling of clinical lung biopsies was done to identify aberrant signaling pathways. ELISA confirmed low circulating protein levels in the patient.</p><p><strong>Findings: </strong>We identified homozygosity of the p.Cys139Arg loss-of-function progranulin (GRN) variant and an alveolar macrophage transcriptomic signature consistent with tumor necrosis factor alpha (TNF-α) pathway activation. This motivated treatment with anti-TNF monoclonal antibodies, resulting in dramatic improvement of the patient's lung and liver disease.</p><p><strong>Conclusions: </strong>These findings demonstrate the clinical utility of convergent multiomics in the evaluation and implementation of precision therapeutics in rare diseases.</p><p><strong>Funding: </strong>This work was supported by a grant from the Chan Zuckerberg Initiative Patient-Partnered Collaboration for single-cell analysis of rare inflammatory pediatric disease, the Corkin Family Fund for Research, and in part by cooperative agreement U01TR002623 from the National Center for Advancing Translational Sciences/NIH and the PrecisionLink Project at Boston Children's Hospital.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100607"},"PeriodicalIF":12.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531955","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":"Ultra-rapid droplet digital PCR enables intraoperative tumor quantification.","authors":"Zachary R Murphy, Emilia C Bianchini, Andrew Smith, Lisa I Körner, Teresa Russell, David Reinecke, Nader Maarouf, Yuxiu Wang, John G Golfinos, Alexandra M Miller, Matija Snuderl, Daniel A Orringer, Gilad D Evrony","doi":"10.1016/j.medj.2025.100604","DOIUrl":"10.1016/j.medj.2025.100604","url":null,"abstract":"<p><strong>Background: </strong>The diagnosis and treatment of tumors often depend on molecular-genetic data. However, rapid and iterative access to molecular data is not currently feasible during surgery, complicating intraoperative diagnosis and precluding measurement of tumor cell burdens at surgical margins to guide resections.</p><p><strong>Methods: </strong>Here, we introduce Ultra-Rapid droplet digital PCR (UR-ddPCR), a technology that achieves the fastest measurement, to date, of mutation burdens in tissue samples, from tissue to result in 15 min. Our workflow substantially reduces the time from tissue biopsy to molecular diagnosis and provides a highly accurate means of quantifying residual tumor infiltration at surgical margins.</p><p><strong>Findings: </strong>We demonstrate UR-ddPCR assays for the IDH1 R132H and BRAF V600E clonal mutations that are present in many low-grade gliomas and melanomas, respectively, and whose intraoperative detection would shape surgical decision-making. We illustrate the clinical feasibility of UR-ddPCR by performing it intraoperatively for 22 brain tumor cases, and we further combine UR-ddPCR tumor cell percentage measurements with UR-stimulated Raman histology intraoperatively to estimate tumor cell densities ranging from >1,300 tumor cells/mm² within a tumor core to <5 tumor cells/mm² at tumor margins. UR-ddPCR measurements were virtually identical to standard ddPCR measurements performed on the same samples (R² = 0.995).</p><p><strong>Conclusions: </strong>The technology and workflow developed here enable intraoperative molecular-genetic assays with unprecedented speed and sensitivity. We anticipate that our method will facilitate novel point-of-care diagnostics and molecularly guided surgeries that improve clinical outcomes.</p><p><strong>Funding: </strong>This study was funded by the National Institutes of Health and NYU Grossman School of Medicine institutional funds. Reagents and instruments were provided in kind by Bio-Rad.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100604"},"PeriodicalIF":12.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516869","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":"Humoral signatures of Caspr2-antibody spectrum disorder track with clinical phenotypes and outcomes.","authors":"Paula Terroba-Navajas, Marianna Spatola, Omar Chuquisana, Bastien Joubert, Juna M de Vries, Andre Dik, Laura Marmolejo, Friederike Jönsson, Gordan Lauc, Stjepana Kovac, Harald Prüss, Heinz Wiendl, Maarten J Titulaer, Jérôme Honnorat, Jan D Lünemann","doi":"10.1016/j.medj.2024.09.004","DOIUrl":"10.1016/j.medj.2024.09.004","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin (Ig) G4 auto-antibodies (Abs) against contactin-associated protein-like 2 (Caspr2), a transmembrane cell adhesion protein expressed in the central and peripheral nervous system, are found in patients with a broad spectrum of neurological symptoms. While the adoptive transfer of Caspr2-specific IgG induces brain pathology in susceptible rodents, the mechanisms by which Caspr2-Abs mediate neuronal dysfunction and translate into clinical syndromes are incompletely understood.</p><p><strong>Methods: </strong>We use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral biosignatures in patients with Caspr2-Ab-associated neurological syndromes.</p><p><strong>Findings: </strong>We identify two signatures strongly associated with two major clinical phenotypes, limbic encephalitis (LE) and predominant peripheral nerve hyperexcitability without LE (non-LE). Caspr2-IgG Fc-driven pro-inflammatory features, characterized by increased binding affinities for activating Fcγ receptors (FcγRs) and C1q, along with a higher prevalence of IgG1-class Abs, in addition to IgG4, are strongly associated with LE. Both the occurrence of Caspr2-specific IgG1 and higher serum levels of interleukin (IL)-6 and IL-15, along with increased concentrations of biomarkers reflecting neuronal damage and glial cell activation, are associated with poorer clinical outcomes at 1-year follow-up.</p><p><strong>Conclusions: </strong>The presence of IgG1 isotypes and Fc-mediated effector functions control the pathogenicity of Caspr2-specific Abs to induce LE. Biologics targeting FcR function might potentially restrain Caspr2-Ab-induced pathology and improve clinical outcomes.</p><p><strong>Funding: </strong>This study was funded by a German-French joint research program supported by the German Research Foundation (DFG) and the Agence Nationale de la Recherche (ANR) and by the Interdisciplinary Centre for Clinical Research (IZKF) Münster.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100515"},"PeriodicalIF":12.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406970","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":"Oral SERDs: Transforming the treatment of advanced breast cancer-Insights from EMBER-3.","authors":"Manuel Alva-Bianchi, Rodrigo Sánchez-Bayona, Eva Ciruelos","doi":"10.1016/j.medj.2025.100602","DOIUrl":"10.1016/j.medj.2025.100602","url":null,"abstract":"<p><p>The phase 3 EMBER-3 trial¹ demonstrated that when compared to standard therapy, imlunestrant improved progression-free survival (PFS) in advanced ER+/HER2- breast cancer with ESR1 mutations. When combined with abemaciclib, it significantly improved PFS for the entire population. However, the absence of a biomarker-based control group limits broader conclusions, highlighting the need for trials incorporating specific standards in ER+/HER2- breast cancer.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 2","pages":"100602"},"PeriodicalIF":12.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426320","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":"Targeting HLA-E-overexpressing cancers with a NKG2A/C switch receptor.","authors":"Michelle Sætersmoen, Ivan S Kotchetkov, Lamberto Torralba-Raga, Jorge Mansilla-Soto, Ebba Sohlberg, Silje Zandstra Krokeide, Quirin Hammer, Michel Sadelain, Karl-Johan Malmberg","doi":"10.1016/j.medj.2024.09.010","DOIUrl":"10.1016/j.medj.2024.09.010","url":null,"abstract":"<p><strong>Background: </strong>Human leukocyte antigen (HLA)-E is overexpressed by a large proportion of solid tumors, including malignant glioblastoma, and acts as a major checkpoint for NKG2A⁺ CD8⁺ T cells and natural killer (NK) cells in the tumor microenvironment and circulation. This axis operates alongside PD-L1 to inhibit effector responses by T and NK cells.</p><p><strong>Methods: </strong>We engineered a chimeric A/C switch receptor, combining the high HLA-E binding affinity of the NKG2A receptor ectodomain with the activating signaling of the NKG2C receptor endodomain. The cytotoxic function of A/C switch-transduced NK and T cells was evaluated against tumor cells with varying levels of HLA-E expression. In vivo efficacy was assessed using a xenograft model of glioblastoma.</p><p><strong>Findings: </strong>A/C switch-transduced NK and T cells exhibited superior and specific cytotoxicity against tumor cells with medium to high HLA-E expression. A/C switch-expressing human T cells demonstrated enhanced anti-tumor function in a glioblastoma xenograft model. The activity of the modified T cells was governed by an equilibrium between A/C switch levels and HLA-E expression, creating a therapeutic window to minimize on-target, off-tumor toxicities. Normal cells remained insensitive to A/C switch T cells, even after interferon (IFN)-γ pretreatment to induce HLA-E expression.</p><p><strong>Conclusions: </strong>The A/C switch receptor effectively targets tumor cells expressing high levels of HLA-E, either alone or in combination with other engineered specificities, to overcome the suppressive NKG2A/HLA-E checkpoint. This approach offers a promising therapeutic strategy with a favorable safety profile for targeting HLA-E-overexpressing tumors.</p><p><strong>Funding: </strong>This work was funded by The Research Council of Norway, the Norwegian Cancer Society, and the National Cancer Institute.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100521"},"PeriodicalIF":12.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476308","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":"The VIVID-1 study: A novel methodological approach provides further evidence of efficacy of selective IL-23 inhibition in Crohn's disease.","authors":"Maria Cappello, Ciro Celsa","doi":"10.1016/j.medj.2024.100572","DOIUrl":"10.1016/j.medj.2024.100572","url":null,"abstract":"<p><p>The VIVID-1 study is a phase 3 randomized controlled trial assessing the efficacy and safety of mirikizumab in moderate-to-severe active Crohn's disease.¹ The study confirms the advantage of selective IL-23 inhibition, while the treat-through design and the choice of composite coprimary endpoints represent an innovative strategy in conducting clinical trials in Crohn's disease.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 2","pages":"100572"},"PeriodicalIF":12.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426332","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":"On-treatment PSA kinetics as a potential biomarker: Guiding personalized treatment in metastatic hormone-sensitive prostate cancer.","authors":"Zeynep Irem Ozay, Chadi Hage Chehade, Neeraj Agarwal","doi":"10.1016/j.medj.2024.10.011","DOIUrl":"10.1016/j.medj.2024.10.011","url":null,"abstract":"<p><p>In this issue of Med, Bian et al. present a post-hoc analysis of the phase 3 CHART trial investigating rezvilutamide in the metastatic hormone-sensitive prostate cancer setting.¹ They show that patients achieving a deep PSA response at six months had significantly improved outcomes. These findings could impact patient counseling and support the potential role of on-treatment PSA kinetics in personalizing therapy.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 2","pages":"100534"},"PeriodicalIF":12.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426316","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}