MedComm最新文献

{"title":"Tripartite Motif Containing 65 Deficiency Confers Protection Against Acute Kidney Injury via Alleviating Voltage-Dependent Anion Channel 1–Mediated Mitochondrial Dysfunction","authors":"Tao Chen,&nbsp;Yang Zhang,&nbsp;Liting Ding,&nbsp;Chenlu Xiong,&nbsp;Chao Mei,&nbsp;Sisi Wei,&nbsp;Ming Jiang,&nbsp;Yingjie Huang,&nbsp;Jianrong Chen,&nbsp;Tao Xie,&nbsp;Qing Zhu,&nbsp;Qi Zhang,&nbsp;Xuan Huang,&nbsp;Shibiao Chen,&nbsp;Yong Li","doi":"10.1002/mco2.70149","DOIUrl":"https://doi.org/10.1002/mco2.70149","url":null,"abstract":"<p>Acute kidney injury (AKI) is a prevalent and serious clinical disease with a high incidence rate and significant health burden. The limited understanding of the complex pathological mechanisms has hindered the development of efficacious therapeutics. Tripartite motif containing 65 (TRIM65) has recently been identified as a key regulator of acute inflammation. However, its role in AKI remains unclear. The present study observed that TRIM65 expression was upregulated in AKI. Moreover, the knockout of the <i>Trim65</i> gene in mice exhibited a substantial protective impact against rhabdomyolysis, ischemia-reperfusion (I/R), and cisplatin-induced AKI. Mechanistically, TRIM65 directly binds and mediates K48/K63-linked polyubiquitination modifications of voltage-dependent anion channel 1 (VDAC1) at its K161 and K200 amino acid sites. TRIM65 plays a role in maintaining the stability of VDAC1 and preventing its degradation by the autophagy pathway. TRIM65 deficiency attenuates mitochondrial dysfunction in renal tubular epithelial cells during AKI. Conversely, the overexpression of VDAC1 in renal tissues has been demonstrated to negate the protective effect of TRIM65 deficiency on AKI. These findings suggest that TRIM65 may play a role regulating of AKI through the targeting of VDAC1-dependent mitochondrial function, offering potential avenues for the development of new drug targets and strategies for the treatment of AKI.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Multiplex Immunohistochemistry and Machine Learning for Glioma Subtyping and Prognosis Prediction","authors":"Houshi Xu,&nbsp;Zhen Fan,&nbsp;Shan Jiang,&nbsp;Maoyuan Sun,&nbsp;Huihui Chai,&nbsp;Ruize Zhu,&nbsp;Xiaoyu Liu,&nbsp;Yue Wang,&nbsp;Jiawen Chen,&nbsp;Junji Wei,&nbsp;Ying Mao,&nbsp;Zhifeng Shi","doi":"10.1002/mco2.70138","DOIUrl":"https://doi.org/10.1002/mco2.70138","url":null,"abstract":"<p>Glioma subtyping is crucial for treatment decisions, but traditional approaches often fail to capture tumor heterogeneity. This study proposes a novel framework integrating multiplex immunohistochemistry (mIHC) and machine learning for glioma subtyping and prognosis prediction. 185 patient samples from the Huashan hospital cohort were stained using a multi-label mIHC panel and analyzed with an AI-based auto-scanning system to calculate cell ratios and determine the proportion of positive tumor cells for various markers. Patients were divided into two cohorts (training: <i>N</i> = 111, testing: <i>N</i> = 74), and a machine learning model was then developed and validated for subtype classification and prognosis prediction. The framework identified two distinct glioma subtypes with significant differences in prognosis, clinical characteristics, and molecular profiles. The high-risk subtype, associated with older age, poorer outcomes, astrocytoma/glioblastoma, higher tumor grades, elevated mesenchymal scores, and an inhibitory immune microenvironment, exhibited IDH wild-type, 1p19q non-codeletion, and MGMT promoter unmethylation, suggesting chemotherapy resistance. Conversely, the low-risk subtype, characterized by younger age, better prognosis, astrocytoma/oligodendroglioma, lower tumor grades, and favorable molecular profiles (IDH mutation, 1p19q codeletion, MGMT promoter methylation), indicated chemotherapy sensitivity. The mIHC-based framework enables rapid glioma classification, facilitating tailored treatment strategies and accurate prognosis prediction, potentially improving patient management and outcomes.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils in Tissue Injury and Repair: Molecular Mechanisms and Therapeutic Targets","authors":"Luying Yang,&nbsp;Fan Shi,&nbsp;Feng Cao,&nbsp;Le Wang,&nbsp;Jianzhen She,&nbsp;Boling He,&nbsp;Xiaoying Xu,&nbsp;Liang Kong,&nbsp;Bolei Cai","doi":"10.1002/mco2.70184","DOIUrl":"https://doi.org/10.1002/mco2.70184","url":null,"abstract":"<p>Tissue repair represents a highly intricate and ordered dynamic process, critically reliant on the orchestration of immune cells. Among these, neutrophils, the most abundant leukocytes in the body, emerge as the initial immune responders at injury sites. Traditionally recognized for their antimicrobial functions in innate immunity, neutrophils now garner attention for their indispensable roles in tissue repair. This review delves into their novel functions during the early stages of tissue injury. We elucidate the mechanisms underlying neutrophil recruitment and activation following tissue damage and explore their contributions to vascular network formation. Furthermore, we investigate the pivotal role of neutrophils during the initial phase of repair across different tissue types. Of particular interest is the investigation into how the fate of neutrophils influences overall tissue healing outcomes. By shedding light on these emerging aspects of neutrophil function in tissue repair, this review aims to pave the way for novel strategies and approaches in future organ defect repair, regeneration studies, and advancements in tissue engineering. The insights provided here have the potential to significantly impact the field of tissue repair and regeneration.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Trispecific Neutralizing Antibodies With Enhanced Potency and Breadth Against Pan-Sarbecoviruses","authors":"Rui Qiao,&nbsp;Yuanchen Liu,&nbsp;Qiyu Mao,&nbsp;Jiayan Li,&nbsp;Yinying Lu,&nbsp;Jialu Shi,&nbsp;Chen Li,&nbsp;Jizhen Yu,&nbsp;Jiami Gong,&nbsp;Xun Wang,&nbsp;Yuchen Shao,&nbsp;Lei Sun,&nbsp;Wenhong Zhang,&nbsp;Hongjie Yu,&nbsp;Hin Chu,&nbsp;Pengfei Wang,&nbsp;Xiaoyu Zhao","doi":"10.1002/mco2.70191","DOIUrl":"https://doi.org/10.1002/mco2.70191","url":null,"abstract":"<p>The ongoing emergence of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the urgent need for developing antivirals targeting both SARS-CoV-2 variants and related sarbecoviruses. To this end, we designed novel trispecific antibodies, Tri-1 and Tri-2, engineered by fusing the single-chain variable fragments (scFvs) of a potent antibody (PW5-570) to the Fc region of “Knob-into-Hole” bispecific antibodies (bsAbs) composed of two distinct broad antibodies (PW5-5 and PW5-535). Compared with the parental antibodies, Tri-1 and Tri-2 displayed enhanced binding affinities to the receptor-binding domains of SARS-CoV, SARS-CoV-2 wild type, and Omicron XBB.1.16, with each arm contributed to the overall enhancement. Furthermore, pseudovirus neutralization assays revealed that Tri-1 and Tri-2 effectively neutralized all tested SARS-CoV, SARS-CoV-2 variants, and related sarbecoviruses (Pangolin-GD, RaTG13, WIV1, and SHC014), demonstrating potency and breadth superior to any single parental antibody. Consistently, Tri-1 and Tri-2 were found to effectively neutralize authentic SARS-CoV and SARS-CoV-2 variants with IC₅₀ values comparable to or better than those of parental antibodies. Taken together, this study highlights the potential effectiveness of Tri-1 and Tri-2 as novel formats for harnessing cross-neutralizing antibodies in the development of multivalent agents to combat both current and future SARS-like coronaviruses.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alopecia Areata: Pathogenesis, Diagnosis, and Therapies","authors":"Tianyou Ma,&nbsp;Tingrui Zhang,&nbsp;Fengze Miao,&nbsp;Jun Liu,&nbsp;Quangang Zhu,&nbsp;Zhongjian Chen,&nbsp;Zongguang Tai,&nbsp;Zhigao He","doi":"10.1002/mco2.70182","DOIUrl":"https://doi.org/10.1002/mco2.70182","url":null,"abstract":"<p>Alopecia areata (AA) is a complex, chronic inflammatory skin disorder characterized by unpredictable, nonscarring hair loss, affecting millions worldwide. Its pathogenesis remains poorly understood, driven by intricate interactions among immune dysregulation, genetic predisposition, and environmental triggers. Despite significant advances in identifying these contributing factors, substantial gaps persist in our understanding of the full spectrum of AA's molecular mechanisms and in the development of effective therapeutic approaches. This review aims to comprehensively explore the immunological, genetic, epigenetic, and environmental factors underlying AA, with a focus on immune-mediated mechanisms. We also evaluate diagnostic approaches and recent advancements in assessing disease severity. Furthermore, the review discusses evolving therapeutic options, including traditional therapies, biologics, small-molecule agents, and emerging treatments. The academic value of this work lies in its synthesis of current knowledge on the multifaceted nature of AA, providing insights for future research and clinical practice. By elucidating the interconnected factors underlying AA, this review seeks to advance both understanding and management of this prevalent, clinically challenging disorder.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota Dysbiosis: Pathogenesis, Diseases, Prevention, and Therapy","authors":"Yao Shen,&nbsp;Nairui Fan,&nbsp;Shu-xia Ma,&nbsp;Xin Cheng,&nbsp;Xuesong Yang,&nbsp;Guang Wang","doi":"10.1002/mco2.70168","DOIUrl":"https://doi.org/10.1002/mco2.70168","url":null,"abstract":"<p>Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut–brain axis, gut–liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of Astrocytic ATP/Adenosine Release in the Hippocampus Cause Cognitive and Affective Disorders: Molecular Mechanisms, Diagnosis, and Therapy","authors":"Peter Illes,&nbsp;Patrizia Rubini,&nbsp;Henning Ulrich,&nbsp;Hai-Yan Yin,&nbsp;Yong Tang","doi":"10.1002/mco2.70177","DOIUrl":"https://doi.org/10.1002/mco2.70177","url":null,"abstract":"<p>The gliotransmitter adenosine 5'-triphosphate (ATP) and its enzymatic degradation product adenosine play a major role in orchestrating in the hippocampus cognitive and affective functions via P2 purinoceptors (P2X, P2Y) and P1 adenosine receptors (A1, A2A). Although numerous reviews exist on purinoceptors that modulate these functions, there is an apparent gap relating to the involvement of astrocyte-derived extracellular ATP. Our review focuses on the following issues: An impeded release of ATP from hippocampal astrocytes through vesicular mechanisms or connexin hemichannels and pannexin channels interferes with spatial working memory in rodents. The pharmacological blockade of P2Y1 receptors (P2Y1Rs) reverses the deficits in learning/memory performance in mouse models of familial Alzheimer's disease (AD). Similarly, in mouse models of major depressive disorder (MDD), based on acute or chronic stress-induced development of depressive-like behavior, a reduced exocytotic/channel-mediated ATP release from hippocampal astrocytes results in the deterioration of these behavioral responses. However, on the opposite, the increased stimulation of the microglial/astrocytic P2X7R-channel by ATP causes neuroinflammation and in consequence depressive-like behavior. In conclusion, there is strong evidence for the assumption that gliotransmitter ATP is intimately involved in the pathophysiology of cognitive and affective neuron/astrocyte-based human illnesses opening new diagnostic and therapeutic vistas for AD and MDD.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Stromal Cells Inside the Tumor Microenvironment of Ovarian Cancer: In Vitro Generation of Cancer-Associated Fibroblast-Like Cells and Their Impact in a 3D Model","authors":"Jacopo Romoli,&nbsp;Paola Chiodelli,&nbsp;Patrizia Bonassi Signoroni,&nbsp;Elsa Vertua,&nbsp;Clarissa Ferrari,&nbsp;Elisabetta Giuzzi,&nbsp;Alice Paini,&nbsp;Elisa Scalvini,&nbsp;Andrea Papait,&nbsp;Francesca Romana Stefani,&nbsp;Antonietta Rosa Silini,&nbsp;Ornella Parolini","doi":"10.1002/mco2.70172","DOIUrl":"https://doi.org/10.1002/mco2.70172","url":null,"abstract":"<p>The tumor microenvironment (TME) is the combination of cells and factors that promotes tumor progression, and cancer-associated fibroblasts (CAFs) are a key component within TME. CAF originates from various stromal cells and is activated by factors such as transforming growth factor-beta (TGF-β) secreted by tumor cells, favoring chemoresistance and metastasis. Recent publications have underlined plasticity and heterogeneity and their strong contribution to the reactive stroma within the TME. Our study aimed to replicate the TME's structure by creating a 3D in vitro model of ovarian cancer (OC). By incorporating diverse tumor and stromal cells, we simulated a physiologically relevant environment for studying CAF-like cell behavior within tumor spheroids in a context-dependent manner. CAF-like cells were generated by exposing human dermal fibroblasts to OC cell line conditioned media in the presence or absence of TGF-β. Herein, we found that different stimuli induce the generation of heterogeneous populations of CAF-like cells. Notably, we observed the ability of CAF-like cells to shape the intratumoral architecture and to contribute to functional changes in tumor cell behavior. This study highlights the importance of precise assessment of CAF for potential therapeutic interventions and further provides a reliable model for investigating novel therapeutic targets in OC.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptomics Revealed E-Cigarettes-Induced Vascular Remodeling by Enhancing Tcf21 Expression","authors":"Ruiyang Ding,&nbsp;Xiaoke Ren,&nbsp;Qinglin Sun,&nbsp;Shiqian liu,&nbsp;Linyuan Huang,&nbsp;Zhiwei Sun,&nbsp;Junchao Duan","doi":"10.1002/mco2.70183","DOIUrl":"https://doi.org/10.1002/mco2.70183","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Electronic cigarettes (e-cigs) are battery-powered new tobacco products attracting wide attention due to their potential to promote smoking cessation and uncertainty in long-term health effects. The global market of e-cigs is still expanding with a compound annual growth rate of 30.6% from 2023 to 2030, and the United States has the largest e-cig market with an e-cig prevalence in 4.5% of adults and 10% of high school students [&lt;span&gt;1, 2&lt;/span&gt;]. Although e-cigs were generally considered safer than canonical tobacco products, the outbreak of vaping-associated lung injury in 2020, which incurred more than 2800 hospital admissions, highlighted their potential threat to human health. According to the scientific statement from the American Heart Association (AHA), e-cig use may impose a latent risk to the cardiopulmonary system, and epidemiological studies suggested that e-cig aerosol could enhance arterial stiffness in humans [&lt;span&gt;3&lt;/span&gt;]. Laboratory evidence suggested that e-cigs could accelerate atherosclerosis and aortic aneurysms in mice [&lt;span&gt;4, 5&lt;/span&gt;], while the exact mechanisms of e-cig-related effects on the vasculature remained largely unknown. Here, we investigate the sub-chronic effects of e-cig aerosol on vascular structure, function, and changes in single-cell transcriptome in mice.&lt;/p&gt;&lt;p&gt;C57BL/6J male mice aged 8 weeks inhaled filtered air (as control) or e-cig (RELX, containing glycerin, propylene glycol, spices, and 3% nicotine) 1 h per day in the exposure chamber for consecutive 90 days (Figure 1A, upper panel). Details about exposure patterns were provided in the Supplementary Information. Hematoxylin and eosin (H&amp;E) staining indicated that sub-chronic exposure to e-cig aerosol increased the media thickness and promoted the vascular smooth muscle cell (VSMC) hyperplasia and disordered arrangement (Figure 1A, lower panel). Verhoeff's Van Gieson (EVG) staining revealed the fractured and distorted distribution of the elastic fibers in mice exposed to e-cig aerosol. Doppler ultrasound assessment indicated that e-cig aerosol exposure reduced the left common carotid artery pulsatility index (LCCA PI) while enhancing the carotid intima-media thickness (CIMT), pulse wave velocity (PWV), left common carotid artery peak systolic velocity (LCCA PSV), and left common carotid artery end-diastolic velocity (LCCA EDV). These results suggested that long-term exposure to e-cig aerosol increased the aortic wall thickness and impaired arterial function.&lt;/p&gt;&lt;p&gt;The whole aorta samples collected from mice were used for single-cell RNA transcriptome sequencing (scRNA-seq), and the raw data was deposited to the Gene Expression Omnibus (GEO), accession number GSE288003. scRNA-seq identified 20 cell clusters in the aorta samples from mice exposed to filtered air or e-cig aerosol, and they could be classified as six cell lineages according to specific markers, including VSMC, endothelial cell, fibroblast-like cell, macropha","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Diagnostics and Therapeutics for Cancer of Unknown Primary in the Era of Precision Medicine","authors":"Ting Zhao,&nbsp;Xiaowei Zhang,&nbsp;Xin Liu,&nbsp;Qifeng Wang,&nbsp;Xichun Hu,&nbsp;Zhiguo Luo","doi":"10.1002/mco2.70161","DOIUrl":"https://doi.org/10.1002/mco2.70161","url":null,"abstract":"<p>Cancer of unknown primary (CUP), a set of histologically confirmed metastases that cannot be identified or traced back to its primary despite comprehensive investigations, accounts for 2–5% of all malignancies. CUP is the fourth leading cause of cancer-related deaths worldwide, with a median overall survival (OS) of 3–16 months. CUP has long been challenging to diagnose principally due to the occult properties of primary site. In the current era of molecular diagnostics, advancements in methodologies based on cytology, histology, gene expression profiling (GEP), and genomic and epigenomic analysis have greatly improved the diagnostic accuracy of CUP, surpassing 90%. Our center conducted the world's first phase III trial and demonstrated improved progression-free survival and favorable OS by GEP-guided site-specific treatment of CUP, setting the foundation of site-specific treatment in first-line management for CUP. In this review, we detailed the epidemiology, etiology, pathogenesis, as well as the histologic, genetic, and clinical characteristics of CUP. We also provided an overview of the advancements in the diagnostics and therapeutics of CUP over the past 50 years. Moving forward, we propose optimizing diagnostic modalities and exploring further-line treatment regimens as two focus areas for future studies on CUP.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}