Clinical and translational discovery最新文献

{"title":"Antibody–drug conjugate combined with chemoimmunotherapy: Redefining the neoadjuvant strategy for human epidermal growth factor receptor 2-overexpressing locally advanced gastric cancer","authors":"Shulun Nie, Cunliang Wang, Xiaolan Cao, Shuyi Song, Yu Wang","doi":"10.1002/ctd2.70159","DOIUrl":"https://doi.org/10.1002/ctd2.70159","url":null,"abstract":"<p>Gastric cancer is one of the malignancies that pose a serious threat to human health worldwide. According to the 2022 global cancer statistics, approximately 968 000 new cases and 660 000 deaths from gastric cancer were reported, ranking fifth in both incidence and mortality among all malignancies.<span><sup>1</sup></span> China bears an especially heavy burden of gastric cancer, with 359 000 newly diagnosed cases and 260 000 deaths in 2022, accounting for 37% and 39% of the global totals, respectively.<span><sup>2</sup></span> Because early-stage disease is often clinically silent, most patients are diagnosed at a locally advanced or metastatic stage, resulting in an extremely poor prognosis. Although conventional cytotoxic chemotherapy can delay disease progression to some extent, its limited efficacy has accelerated the development of precision treatment strategies based on molecular classification in gastric cancer. Human epidermal growth factor receptor 2 (HER2) is one of the most clinically relevant and therapeutically actionable biomarkers in gastric cancer, with HER2 positivity detected in approximately 15% of gastric cancer.<span><sup>3</sup></span> HER2-positive gastric cancer is typically associated with increased tumour aggressiveness and inferior clinical outcomes.<span><sup>4</sup></span> Although trastuzumab plus chemotherapy has become the standard first-line regimen for advanced HER2-positive gastric cancer, the optimal perioperative and neoadjuvant treatment strategy for this subgroup remains undefined. Moreover, pathological response rates in previous exploratory studies have remained unsatisfactory; notably, the NEOHX trial reported a pathological complete response (pCR) rate of only 9.6% with perioperative trastuzumab combined with XELOX,<span><sup>5</sup></span> whereas neoadjuvant trastuzumab deruxtecan monotherapy in the EPOC2003 study achieved a pCR rate of merely 3.7% and a major pathological response (MPR) rate of 14.8%.<span><sup>6</sup></span> Accordingly, the development of more effective perioperative and neoadjuvant regimens aimed at improving R0 resection rates, reducing recurrence risk and enhancing long-term survival remains a major unmet clinical need.</p><p>Against this background, the study by Wang et al.<span><sup>7</sup></span> provides encouraging preliminary evidence for addressing these therapeutic challenges. The authors reported a novel triplet regimen consisting of the HER2-targeted antibody–drug conjugate (ADC) disitamab vedotin (DV, RC48), the programmed death-1 (PD-1) inhibitor camrelizumab and the oral fluoropyrimidine S-1 as neoadjuvant therapy for HER2-overexpressing locally advanced gastric or gastroesophageal junction (G/GEJ) cancer. Among the 24 patients who subsequently underwent D2 gastrectomy, the pCR rate reached 25.0%, the MPR rate was 45.8%, and the R0 resection rate was 100%; in the full analysis set, the objective response rate (ORR) reached 80.0%. Compared with previously reported","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282376","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":"Current advances in liposome–extracellular vesicle hybrid systems for cancer drug delivery","authors":"Arina Habibi,&nbsp;Mohana Sakhti,&nbsp;Touraj Ahmadi Jouybari,&nbsp;Parnian Yavari,&nbsp;Reza Mozafari,&nbsp;Gelavizh Rostaminasab,&nbsp;Shima Rahmati","doi":"10.1002/ctd2.70162","DOIUrl":"https://doi.org/10.1002/ctd2.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hybrid nanovesicles that combine elements of liposomes and extracellular vesicles (EVs) create a versatile platform for cancer therapy. These systems aim to overcome important limitations of their parent platforms, such as scalability, specificity and stability. They do this by combining the strength and drug-loading ability of synthetic liposomes with the natural targeting and immune-modulating functions of EVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Body</h3>\u0000 \u0000 <p>Recent progress in preparation methods, such as controlled membrane fusion techniques and microfluidic-assisted assembly, has allowed for better encapsulation and improved drug delivery performance. These hybrid systems have shown greater tumour targeting, lower overall toxicity and promising uses in cancer immunotherapy during preclinical studies. Their potential is especially significant in developing cell-free vaccine strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Even though challenges remain in large-scale production, consistency from batch to batch, and meeting regulations, new evidence points to their promise as next-generation platforms for more effective and personalised cancer treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282264","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":"Tipping point and molecular mechanism of the transformation of lung adenocarcinoma in situ to invasive adenocarcinoma: A study based on dynamic network markers in systems biology","authors":"Lin Shi,&nbsp;Longfu Zhang,&nbsp;Jiebai Zhou,&nbsp;Dawei Yang,&nbsp;Mingxiang Feng,&nbsp;Yong Zhang","doi":"10.1002/ctd2.70161","DOIUrl":"https://doi.org/10.1002/ctd2.70161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung adenocarcinoma in situ (AIS), characterised by ground-glass nodules as observed in computed tomography imaging, generally demonstrates a relatively inert biological behaviour and exhibits slow growth rates. Upon transitioning to invasive adenocarcinoma (IAC), the growth rate significantly increases. The molecular mechanisms governing this transformation remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study employed the dynamic network marker (DNB) approach grounded in systems biology to analyse transcriptomic sequencing data from 30 lung nodules including one case of atypical adenomatous hyperplasia, eight cases of AIS, 10 cases of minimally invasive adenocarcinoma (MIA) and 11 cases of IAC and their corresponding 30 adjacent normal tissues from 21 patients were analysed. The primary objective was to elucidate the tipping point and biological mechanisms involved in the progression of lung AIS to IAC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We successfully constructed a dynamic gene expression network linking lung AIS, MIA and IAC. A total of 144 key differential genes were identified, establishing MIA as the critical tipping point for transformation. Furthermore, our findings underscored the significance of pyruvate metabolism in relation to metabolic enzyme genes such as PKLR and LDHAL6A, the metabolic regulation of tumour cells reflecting the Warburg effect during the invasive transformation of lung AIS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that the DNB-based approach to identify the tipping point (MIA stage) and associated key genes and pathways in the invasive transformation of lung adenocarcinoma, providing a novel systems biology perspective for dynamic risk monitoring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282265","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":"Qingdainone, a novel bioactive compound in Realgar‒Indigo naturalis, induced apoptosis and differentiation in ATRA-sensitive and -resistant acute promyelocytic leukaemia cells","authors":"Pengcheng Xu,&nbsp;Yang Ou,&nbsp;Xin Tan,&nbsp;Lili Ji,&nbsp;Yanxia Zhan,&nbsp;Pu Chen,&nbsp;Hao Chen,&nbsp;Yunfeng Cheng","doi":"10.1002/ctd2.70164","DOIUrl":"https://doi.org/10.1002/ctd2.70164","url":null,"abstract":"<p>Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid leukaemia with high mortality rates. The Realgar‒Indigo naturalis formula (RIF), a traditional Chinese medicine, shows promise in APL treatment, but its mechanisms remain unclear. The active compounds in RIF were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissTarget databases. Intersection targets between APL-related genes and RIF targets were analysed using the STRING database and Cytoscape. Molecular docking was performed using CB-Dock to evaluate the binding affinity of Qingdainone to key targets. Cell viability, apoptosis and differentiation were assessed in NB4 and NB4-R1 cells treated with Qingdainone by cell counting kit-8 assay and flow cytometry. Network pharmacology identified Qingdainone as a key bioactive compound in RIF. Molecular docking showed strong binding affinities of Qingdainone to targets such as CCND1, CDK1, CDK4, CASP3 and CASP7. In vitro experiments demonstrated that Qingdainone inhibited proliferation, induced G0/G1-phase arrest, and promoted apoptosis in both all-trans retinoic acid (ATRA)-sensitive and -resistant APL cells. Furthermore, Qingdainone induced differentiation in NB4 and NB4-R1 cells, as evidenced by increased expression of CD11b, CD11c and CD14. Qingdainone from RIF shows potent anti-leukaemic effects by inhibiting proliferation, inducing apoptosis and promoting differentiation in APL cells. The present study highlighted Qingdainone as a potential therapeutic agent, especially for ATRA-resistant cases, and offered insights into mechanisms of RIF in APL treatment.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282323","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":"Epigenetic evolution of bladder cancer from cellular origin to clinical translation","authors":"Kaiyu Qian,&nbsp;Zilin Xu,&nbsp;Zhizhuang Chen,&nbsp;Mengxue Yu,&nbsp;Hongwei Peng,&nbsp;Fangjin Chen,&nbsp;Gang Wang,&nbsp;Yu Xiao,&nbsp;Lingao Ju","doi":"10.1002/ctd2.70166","DOIUrl":"https://doi.org/10.1002/ctd2.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bladder cancer remains difficult to manage because of extensive intratumoral heterogeneity, frequent recurrence, and variable response to standard treatment. The conventional view, which centres on the progressive accumulation of genetic mutations, does not adequately explain how tumours adapt under therapeutic pressure or why clinically distinct subtypes emerge from a shared urothelial origin. Recent single-cell and epigenomic studies indicate that cellular plasticity and chromatin reprogramming substantially shape disease behaviour, prompting a reassessment of how progression and resistance should be modelled.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This mini-review synthesises recent work that combines single-cell chromatin accessibility profiling, DNA methylation analysis, and computational lineage inference to dissect the cellular origins and evolutionary trajectories of bladder cancer. We examine evidence that muscle-invasive and non-muscle-invasive disease may arise from distinct urothelial cell populations, and that a TM4SF1-positive cancer subpopulation acts as a stem-like reservoir contributing to phenotypic diversification, therapeutic resistance, and metastatic competence. We then describe the molecular machinery proposed to sustain this plastic cell state, including androgen receptor and FOXA1 cooperation in enhancer remodelling, the conceptual separation of driver and passenger differentially methylated regions, and the POLD1 to MYC axis that stabilises oncogenic transcription. We further examine two translational outputs that have been built on this mechanistic foundation: a urine tumour DNA methylation assay developed for non-invasive detection, risk stratification, and postoperative surveillance, and a conditionally reprogrammed cell platform that supports patient-derived ex vivo drug sensitivity screening across urological cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Framing bladder cancer as an epigenetically driven evolutionary process helps explain how heterogeneity arises and persists, and identifies clinically useful tools that complement existing genetic and pathological approaches. Prospective multi-institutional validation of the urine methylation assay, panel refinement to improve sensitivity in low-grade disease, and outcome-linked drug sensitivity studies based on conditionally reprogrammed cells will determine the extent to which this framework can inform precision oncology in bladder cancer and serve as a template for other epithelial malignancies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282266","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":"TGF-β1-driven epithelial‒mesenchymal transition mediates the fibrotic process in IgG4-related disease","authors":"In-Woon Baek,&nbsp;Kyung-Su Park,&nbsp;Ki-Jo Kim","doi":"10.1002/ctd2.70160","DOIUrl":"https://doi.org/10.1002/ctd2.70160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Major challenges exist in understanding the pathogenic mechanisms and developing systemic therapeutic strategies for IgG4-related disease (IgG4-RD) due to its rarity, unique clinical manifestations and inconsistent response to specific treatments. To overcome these limitations, comprehensive analysis of gene expression profiles may serve as a crucial stepping stone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A salivary gland transcriptomic dataset encompassing both bulk tissue and single-cell levels was obtained. Cellular and molecular features were identified by analysing differentially expressed genes and performing functional enrichment analyses. Gene regulatory and cell‒cell communication analyses were also conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most enriched processes were the epithelial‒mesenchymal transition (EMT) and extracellular matrix organisation. EMT, which was weighted towards a mesenchymal signature, was closely associated with myofibroblasts, extracellular matrix organisation and the transforming growth factor-β (TGF-β) signalling pathway. Fibroblasts were the primary cell subset enriched for in the EMT signature. Additionally, CD19⁺ B cells, cytotoxic T cells and regulatory T cells were the main sources of TGF-β1. In the analysis of B cell‒fibroblast communication, EMT of fibroblasts was found to be activated primarily by TGF-β1 secreted from CD19⁺ B cells. Reciprocally, fibroblasts supported CD19⁺ B cells via CXCL14‒CXCR4 and CXCL12‒CXCR4 interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest a pivotal role for TGF-β1-mediated EMT in the pathogenesis of fibrosis associated with IgG4-RD, with CD19⁺ B cells identified as a significant source of TGF-β1. This evidence substantiates the rationale for B-cell-depletion therapy as a promising therapeutic strategy for this condition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282054","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":"Nanorobotic platforms for targeted drug delivery: Materials engineering, functional dynamics, and biomedical translation","authors":"Mohd Shoab Ali,&nbsp;Garima Gupta,&nbsp;Khang Wen Goh,&nbsp;Rahul Shukla,&nbsp;Amirhossein Sahebkar,&nbsp;Prashant Kesharwani","doi":"10.1002/ctd2.70157","DOIUrl":"https://doi.org/10.1002/ctd2.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nanorobotic systems represent an emerging and disruptive paradigm in nanomedicine for precision drug delivery, controlled therapeutic release, and minimally invasive biomedical interventions. Recent advances in materials engineering, bioinspired design, and external actuation techniques have greatly improved the functionality, navigation, and targeting capabilities of nanorobots for biomedical applications in recent years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This review aims to give a comprehensive overview of the major classes of nanorobotic systems, their propulsion mechanisms, biomedical applications, safety considerations, and translational potential in drug delivery and therapeutic interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A critical review of recent literature was carried out to evaluate various nanorobotic platforms including DNA-based, magnetic, catalytic, biohybrid, ultrasound-driven, light-responsive and stimuli-responsive nanorobots. Their composition, propulsion mechanism, functional dynamics and therapeutic performance were studied systematically.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nanorobotic systems have shown great potential for targeted drug delivery, site-specific therapeutic release, enhanced tissue penetration, and improved treatment precision. The comparative analysis has revealed the differences between the nanorobotic platforms in terms of controllability, biocompatibility, targeting efficiency and translational feasibility. However, a number of challenges remain including biodistribution, immune recognition, reticuloendothelial system clearance, long-term toxicity, biodegradability, large-scale manufacturing and regulatory approval.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Nanorobotic systems have shown great potential for targeted drug delivery, site-specific therapeutic release, enhanced tissue penetration, and improved treatment precision. The comparative analysis has revealed the differences between the nanorobotic platforms in terms of controllability, biocompatibility, targeting efficiency and translational feasibility. However, a number of challenges remain including biodistribution, immune recognition, reticuloendothelial system clearance, long-term toxicity, biodegradability, large-scale manufacturing and regulatory approval.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148237415","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":"VSMC phenotypic switching in thoracic aortic aneurysm at single-cell resolution: Trajectories, regulatory circuits, and spatial niches","authors":"Zehua Shao,&nbsp;Chunguang Guo,&nbsp;Zhongyuan Lu,&nbsp;Jianyang Liu,&nbsp;Hao Tang,&nbsp;Hongwei Guo,&nbsp;Zhidong Zhang","doi":"10.1002/ctd2.70150","DOIUrl":"https://doi.org/10.1002/ctd2.70150","url":null,"abstract":"<p>Thoracic aortic aneurysm (TAA) is a life-threatening cardiovascular disorder characterized by progressive aortic dilation that often culminates in dissection or rupture, with few effective pharmacological interventions currently available. Vascular smooth muscle cells (VSMCs)-the predominant cellular component of the aortic media-undergo extensive phenotypic modulation during TAA development. However, the heterogeneity of VSMC populations and the molecular mechanisms regulating their fate decisions remained poorly understood until the emergence of single-cell technologies. Single-cell RNA sequencing, single-nucleus assay for transposase-accessible chromatin sequencing, and spatial transcriptomics have revolutionized the understanding of VSMC diversity at an unprecedented resolution. These approaches have revealed a complex spectrum of VSMC phenotypic states that extend beyond the classical contractile–synthetic dichotomy, including fibroblast-like, macrophage-like, and chondrocyte-like subpopulations that arise through distinct differentiation trajectories. This review systematically summarizes recent progress in elucidating VSMC phenotypic switching in TAA, emphasizing developmental trajectories reconstructed through pseudotime analyses, the gene regulatory networks controlling fate decisions, and the spatial microenvironmental cues influencing VSMC behaviour. Furthermore, it discusses the translational implications of these insights for identifying novel diagnostic biomarkers and developing therapeutic strategies aimed at stabilizing VSMC phenotypes.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148237411","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":"Clinical significance of urinary SPP1 as a potential new diagnostic marker for oesophageal squamous cell carcinoma","authors":"Bingrong Guo,&nbsp;Jiawei Zhang,&nbsp;Jianpeng Che,&nbsp;Yuan Zhong,&nbsp;Linlin Ji,&nbsp;Wei Li","doi":"10.1002/ctd2.70155","DOIUrl":"https://doi.org/10.1002/ctd2.70155","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Urinary proteins could be useful as noninvasive biomarkers for the detection of oesophageal squamous cell carcinoma (ESCC). We assessed the levels of secreted phosphoprotein 1 (SPP1) in urine samples from patients with ESCC and evaluated its potential as a diagnostic biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Urinary SPP1 levels were measured in 29 ESCC patients and 30 healthy controls using an enzyme-linked immunosorbent assay. SPP1 expression was subsequently examined in tumour tissues and paired peritumoural normal tissue from the patients via immunohistochemistry. The diagnostic performance of SPP1 for ESCC was evaluated using receiver operating characteristic curve analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Urinary SPP1 levels were significantly higher in the ESCC group than in the control group. This parameter demonstrated discriminatory power between the groups, with an area under the curve of 0.7. Furthermore, immunohistochemical analysis confirmed that SPP1 expression was markedly upregulated in ESCC tissues compared with that in paired normal tissues. Moreover, subgroup analysis revealed that urinary SPP1 also effectively identified patients with stage III ESCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study suggests that urinary SPP1 may serve as a novel biomarker for the detection of ESCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174130","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 3","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148091487","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}