Clinical and Experimental Medicine最新文献

{"title":"CDK9 and hematologic malignancies: pioneering novel therapeutic approaches.","authors":"Hanie Raufi, Pouya Zahmatkesh, Sahar Safaei, Ata Bahadori, Saeed Solali","doi":"10.1007/s10238-026-02141-3","DOIUrl":"10.1007/s10238-026-02141-3","url":null,"abstract":"<p><p>cyclin-dependent kinase 9 (CDK9) A key regulator of transcriptional elongation influences the transcription of oncogenes and anti-apoptotic proteins. Within the context of the positive transcription elongation factor b (P-TEFb) complex, CDK9 facilitates the phosphorylation of the C-terminal domain of RNA polymerase II. It also contributes to epigenetic regulation by phosphorylating histones and altering chromatin accessibility, thereby sustaining the transcription of oncogenic programs. This mechanism initiates the transcription of genes that are crucial for the proliferation and survival of cancer cells. A variety of hematological malignancies, including acute myeloid leukemia (AML), multiple myeloma (MM), and diffuse large B-cell lymphoma (DLBCL), have been associated with dysregulated CDK9 activity, which sustains oncogene expression and contributes to resistance to treatment. A notable therapeutic approach focuses on the inhibition of CDK9. This method may function as a therapeutic strategy that exploits the transcriptional addiction of malignant cells to short-lived oncogenic transcripts. By targeting a central regulator of transcriptional elongation, this approach selectively disrupts the sustained expression of survival-critical proteins such as MCL-1 and MYC, thereby exposing a therapeutic vulnerability in hematologic malignancies. Promising outcomes in preclinical and early clinical studies have been achieved by developing selective and pharmacokinetically more effective CDK9 inhibitors. Candidates for the combination of conventional chemotherapeutic drugs with other targeted therapy modalities. Research findings indicate that innovative CDK9 inhibitors and the silencing of CDK9 through siRNA may drastically change the therapeutic approach to hematological malignancies, particularly for patients facing recurrence or resistance to prior treatments. This review focuses primarily on hematologic malignancies because they exhibit pronounced transcriptional addiction to short-lived super-enhancer-driven transcripts (MYC, MCL-1), making CDK9 inhibition particularly effective. In contrast, solid tumors often display greater microenvironmental heterogeneity and compensatory pathways that limit single-agent efficacy.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analysis and experimental validation of dioxin-interacting genes reveal diagnostic and prognostic biomarkers in lung adenocarcinoma.","authors":"Guofang Yin, Bo Li, Shiming Fan, Zhiguo Wang, Qilan Jiang, Fang He, Hongli Cao, Yuling Liang, Ying Luo, Feng Jiang, Xianming Fan","doi":"10.1007/s10238-026-02187-3","DOIUrl":"10.1007/s10238-026-02187-3","url":null,"abstract":"<p><p>Dioxins are persistent environmental pollutants and key components of the human exposome with established carcinogenic potential. As airborne toxicants, they link environmental pollution to lung adenocarcinoma (LUAD), yet their molecular mechanisms remain unclear. Dioxin-interacting genes were curated from toxicogenomic databases and intersected with LUAD differentially expressed genes to identify dioxin-related molecular signatures. Consensus clustering was performed to define LUAD subtypes with distinct clinical and transcriptomic characteristics. Weighted gene co-expression network analysis (WGCNA) was applied to identify key gene modules associated with dioxin exposure and tumor progression. Hub genes were further integrated into diagnostic and prognostic models using multiple machine-learning algorithms based on both tumor tissue and peripheral blood transcriptomic datasets. Genome-exposome interactions were explored through pathway enrichment and chemical-gene interaction analyses. Single-cell RNA sequencing data were used to characterize cell-type-specific expression patterns. In vitro functional assays were conducted to validate the biological roles of candidate genes. Both models demonstrated robust predictive performance across cohorts. SLC15A2 was consistently identified as a hub gene and showed predominant expression in lung epithelial cells based on single-cell RNA sequencing. Pan-cancer analyses revealed significant dysregulation of SLC15A2, with lower expression in LUAD associated with poorer survival. Functional experiments confirmed that SLC15A2 overexpression suppressed LUAD cell proliferation and invasion, supporting a tumor-suppressive role. This integrative exposome-genome analysis highlights dioxin-related transcriptomic dysregulation in LUAD and identifies SLC15A2 as a potential tumor suppressor and biomarker for precision stratification.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of deep learning-based multimodal data integration of lung cancer.","authors":"Ya Qin, Simin Wang, Dan Wu, Yanhua Fei, Weiping Ding, Qiong Wang, Runwei Guan, Xiao Liang","doi":"10.1007/s10238-026-02184-6","DOIUrl":"10.1007/s10238-026-02184-6","url":null,"abstract":"<p><p>This is a narrative review that provides a perspective on the recent advances in deep learning (DL)-driven multimodal data integration for lung cancer. Lung cancer remains the most prevalent malignancy and the leading cause of cancer-related mortality worldwide. Despite growing awareness and therapeutic innovations, the majority of cases are diagnosed at advanced stages, resulting in persistently poor survival rates. In recent years, artificial intelligence (AI) has demonstrated transformative potential in oncology research, particularly through the integration of heterogeneous biomedical data modalities. The fusion of radiological imaging, histopathological slides, genomic and transcriptomic profiles, and electronic health records has consistently outperformed unimodal approaches by capturing complementary biological and clinical information. DL-based multimodal integration frameworks have shown promise in improving diagnostic accuracy, stratifying patients according to therapeutic response, and predicting long-term prognosis, thereby contributing to precision oncology. By leveraging the synergistic strengths of diverse data sources, multimodal AI models can enable more accurate and individualized strategies for diagnosis, treatment planning, and longitudinal disease monitoring, ultimately improving clinical outcomes for patients with lung cancer.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSMC2 promotes hepatocellular carcinoma progression through interaction with EGFR.","authors":"Yecheng Li, Qunxue Su, Zhenyu Feng, Hui Xu, Tengfei He","doi":"10.1007/s10238-026-02178-4","DOIUrl":"10.1007/s10238-026-02178-4","url":null,"abstract":"<p><p>Growing evidence highlights the critical involvement of the ubiquitin-proteasome system in cancer development. As an essential component of the 26 S proteasome, Proteasome 26 S Subunit ATPase 2 (PSMC2) has been implicated in various malignancies, but its role in hepatocellular carcinoma (HCC) progression remains poorly understood. We analyzed PSMC2 expression using The Cancer Genome Atlas database (TCGA) database, and validated findings in clinical HCC specimens and cell lines through immunohistochemistry (IHC) and Western blot. Functional assays (CCK-8, colony formation, Scratch test and transwell invasion assay) were performed to assess the oncogenic properties of PSMC2 in the progression of HCC. Mechanistic studies employed co-immunoprecipitation, Western blot, immunofluorescence and in vivo xenograft models to investigate PSMC2-EGFR interactions and downstream signaling. PSMC2 was significantly overexpressed in HCC tissues and correlated with poor patient prognosis. Genetic knockdown of PSMC2 inhibited HCC cell proliferation, migration, and invasion in vitro, while suppressing tumor growth in vivo. Conversely, PSMC2 overexpression enhanced malignant phenotypes. Mechanistically, PSMC2 physically interacted with EGFR, stabilizing EGFR protein levels and enhancing phosphorylation of downstream AKT and ERK1/2 pathways. Our study identifies PSMC2 as a novel regulator of HCC progression through EGFR-AKT/ERK1/2 signaling axis activation. These findings position PSMC2 as both a prognostic biomarker and a potential therapeutic target for HCC intervention.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma exosome lncRNA panel as a non-invasive biomarker for molecular diagnosis of systemic lupus erythematosus.","authors":"Zhi Li, Shujun Wan, Xueqin Li, Hui Yang, Kun Lv, Xiaolong Zhu, Mengying Zhang","doi":"10.1007/s10238-026-02180-w","DOIUrl":"10.1007/s10238-026-02180-w","url":null,"abstract":"<p><p>Exosome-derived long non-coding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers in various diseases. However, their diagnostic potential in systemic lupus erythematosus (SLE) remains largely unexplored. This study aimed to characterize plasma exosomal lncRNA profiles and identify candidate lncRNAs with diagnostic and disease-monitoring potential in SLE. Plasma exosomes were isolated from SLE patients and healthy controls (HCs), followed by high-throughput sequencing to characterize exosomal lncRNA expression profiles. Differentially expressed lncRNAs were identified and subsequently validated using quantitative real-time PCR (qRT-PCR). Correlations between the validated exosomal lncRNAs and clinical indicators of SLE were assessed. Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed to evaluate the diagnostic performance of the identified lncRNAs. Three plasma-derived exosomal lncRNAs-ENSG00000229882, MIR4713HG, and LINC00620-were significantly upregulated in SLE patients compared with HCs. Logistic regression analysis identified MIR4713HG and LINC00620 as predictors of SLE. A combined diagnostic model incorporating these two lncRNAs demonstrated diagnostic capacity for distinguishing SLE patients from HCs, with an area under the curve (AUC) of 0.759. Notably, exosomal LINC00620 expression was significantly upregulated in patients with active SLE compared with those with inactive disease and showed a positive correlation with SLE Disease Activity Index 2000 (SLEDAI-2 K scores). Plasma exosomal ENSG00000229882, MIR4713HG, and LINC00620 were significantly upregulated in SLE, indicating their potential as non-invasive diagnostic biomarkers. Particularly, LINC00620 showed a positive correlation with disease activity, suggesting its clinical utility for both SLE diagnosis and disease monitoring.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tacrolimus has better performance in B cell reconstitution after allo-HSCT compared to cyclosporine A: a real-world study.","authors":"Hao Zhou, Guangyu Zhou, Wenqiong Xiang, Guilin Ren, Xi Dou, Jianbin Chen, Xiaoqiong Tang, Hongbin Zhang, Xin Wang, Xiaohua Luo, Lin Liu, Li Wang","doi":"10.1007/s10238-026-02176-6","DOIUrl":"10.1007/s10238-026-02176-6","url":null,"abstract":"<p><p>B-cell reconstitution is closely associated with prognosis, infection risk, and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of different calcineurin inhibitors (CNIs) on B-cell recovery remains unclear. We retrospectively analyzed 312 allo-HSCT recipients receiving cyclosporine (CsA, n = 211) or tacrolimus (FK506, n = 101). B-cell proportions in bone marrow and peripheral lymphocyte subsets were compared, and propensity score matching was applied to balance confounders. Multivariate analysis demonstrated that FK506 was independently associated with superior B-cell reconstitution at 3 months (OR 2.93, 95% CI 1.49-5.76, p = 0.010) and 4 months post-transplant (OR 3.53, 95% CI 1.11-11.15, p = 0.024). Higher B-cell proportions at 3-5 months were associated with a significantly lower risk of viral infection. Mediation analysis further revealed that improved B-cell reconstitution at day + 90 partially mediated the protective effect of FK506 against viral infection. These findings suggest that FK506 promotes improved B-cell recovery and may reduce viral infection risk after allo-HSCT.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Myeloma in Children and Young Adults: A Systematic Literature Review.","authors":"Georgia Poultsaki, Theodoros P Vassilakopoulos, Evangelos Terpos, Vassilios Papadakis","doi":"10.1007/s10238-026-02148-w","DOIUrl":"10.1007/s10238-026-02148-w","url":null,"abstract":"<p><p>Multiple myeloma (MM) is extremely rare in pediatric and young adult populations, and its clinical characteristics, therapeutic strategies, and outcomes remain poorly defined. This systematic review consolidates all published cases of MM in patients aged ≤ 25 years, aiming to define epidemiology, presentation, treatment, and theraupeutic outcomes. A systematic literature search was conducted in PubMed up to December 31, 2024, to identify case reports and series of MM in patients ≤ 25 years. Articles lacking patient-specific data, definitive diagnostic criteria, or full English text were excluded. Data on demographics, clinical features, cytogenetics, treatment regimens, and outcomes were extracted. Forty-two patients were included from 33 publications, with a median age of 17 years (range 8-25). Male predominance was noted (M: F = 1.47:1). Common presenting features included bone pain (42.9%) and neurological symptoms (21.4%). IgG myeloma was most frequent, followed by IgA, light-chain only and IgD subtypes. Plasmacytomas were observed in 61.9%, including 30.8% with extramedullary and 57.7% with paramedullary involvement. Cytogenetic abnormalities were detected in 75% of evaluable patients. First-line therapy varied by era, with regimens including conventional chemotherapy, novel agents, and hematopoietic stem cell transplantation (HSCT). Among the 16 patients with evaluable treatment response, the overall response rate to first-line therapy was 75%. Hematopoietic stem cell transplantation (HSCT) was performed in 10 patients and was associated with deeper treatment responses. Contemporary therapeutic regimens were generally well tolerated, and no therapy-related mortality was reported. MM in patients aged ≤ 25 years is a rare clinical entity that may present with distinctive features, including a high frequency of plasmacytomas and extramedullary disease. Modern treatment strategies incorporating novel agents and HSCT appear feasible and effective in this population. Further collaborative studies are required to better define the biological characteristics and optimal management of MM in very young patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of mRECIST tumor response at firstfollow-up after DEB-TACE using a combined radiomics-clinical model and explainability methods.","authors":"Jiayi Yang, Yue Hu, Xinyu He, Qinglong Zhao, Jiahui Wang, Fei Wang, Zhongxing Shi, Hongfei Liu, Wen Lü, Liming Cui","doi":"10.1007/s10238-026-02177-5","DOIUrl":"10.1007/s10238-026-02177-5","url":null,"abstract":"<p><p>To investigate the value of preoperative enhanced computed tomography (CT) radiomics combined with clinical features in predicting the tumor response according to mRECIST of initial drug-eluting bead transarterial chemoembolization (DEB-TACE) in hepatocellular carcinoma (HCC) patients by utilizing the Shapley additive explanations (SHAP) algorithm for model interpretation. A retrospective analysis was conducted on 110 patients. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Radiomic features were extracted from arterial phase computed tomography images and reduced using the least absolute shrinkage and selection operator. These features were combined with clinical indicators to construct predictive models, including logistic regression, naive Bayes, support vector machine, random forest, and XGBoost. The model performance was evaluated using the area under the curve, calibration curve, and decision curve. The combined model showed optimal predictive performance, with area under the curve values of 0.838 and 0.802 for the training and test sets, respectively, statistically outperforming the single models (DeLong test, P < 0.05).Furthermore, SHAP analysis revealed key predictors and their directional effects. Preoperative enhanced computed tomography radiomics combined with clinical indicators can effectively predict the initial tumor response to DEB-TACE. SHAP visualization analysis enhances interpretability and identifies key predictors, offering support for precise treatment and individualized decision-making.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bortezomib synergizes with homoharringtonine in FLT3-ITD-relapsed/refractory acute myeloid leukemia by inducing FLT3-ITD protein degradation.","authors":"Ming Wei, Furong Wang, Dan Huang, Zhijie Kang, Yan Yang, Chengtao Zhang, Jiacheng Lou, Jinsong Yan","doi":"10.1007/s10238-026-02182-8","DOIUrl":"10.1007/s10238-026-02182-8","url":null,"abstract":"<p><p>Mutations in Fms-like tyrosine kinase 3 (FLT3) are strongly associated with relapse and resistance in acute myeloid leukemia (AML) patients, and the treatment of relapsed or refractory AML (R/R AML) remains a major clinical challenge. We previously conducted a prospective clinical trial on R/R AML with chemotherapy regimen BHA (bortezomib, homoharringtonine and cytarabine), which demonstrated promising efficacy in patients with FLT3-mutated R/R AML. However, the therapeutic mechanism remains unclear. In this study, we aim to elucidate the therapeutic mechanism of BHA regimen on the basis of its efficacy for FLT3-mutated R/R AML. We retrospectively analyzed twenty-nine patients with R/R AML, after one course of therapy, patients harboring FLT3 mutations had a significantly higher complete remission/complete remission with incomplete hematologic recovery rate than those without FLT3 mutations (46.67% vs. 7.14%, respectively; P = 0.035). To further explore the underlying mechanisms, we conducted combination index analysis, inhibition of proliferation and apoptosis assays. Compared with 293 T-FLT3 cells, 293 T-FLT3-ITD cells were more sensitive to bortezomib, with significantly lower IC50 values. Bortezomib in combination with homoharringtonine had a synergistic effect on FLT3-ITD cells. Moreover, compared with monotherapy, the combination of bortezomib (4 nM) and homoharringtonine (1 nM) markedly increased total cell death in FLT3-ITD cell lines (MV4-11 and Molm-13). Mechanistically, bortezomib promoted the degradation of FLT3-ITD protein, and the degradation of FLT3-ITD protein was further enhanced by homoharringtonine. Notably, this degradation effect was partially reversed by chloroquine. These findings demonstrate that bortezomib and homoharringtonine have synergistic effects and lead to degradation of FLT3-ITD oncoprotein, potentially contributing to a higher complete remission rate in FLT3-ITD R/R AML.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A microfluidic lung cancer-vascular tumor-on-a-chip model for precise evaluation of anti-invasion therapeutics.","authors":"Jinnuo Lu, Yixiao Huang, Shujie Ma, Shoucheng Hu, Linhua Xuzhan, Yifan Huang, Bowen Wu, Zekai Hu, Chenyou Zhao, Jiayi Huang, Baoao Tan, Xinhao Liu, Zhaobin Guo","doi":"10.1007/s10238-026-02185-5","DOIUrl":"10.1007/s10238-026-02185-5","url":null,"abstract":"<p><p>Lung cancer remains the single leading cause of cancer-related incidence and mortality worldwide, with approximately 90% of all cancer-related deaths due to tumor invasion and metastasis. However, traditional in vitro and animal models are not able to accurately replicate the biologically complex tumor microenvironment; therefore, they limit the exact evaluation of anti-invasion therapies. In the present study, we designed, fabricated and characterized a lung cancer-vascular tumor-on-a-chip utilizing microfluidic technology following previous studies to replicate tumor growth, invasion and interactions with the extracellular matrix (ECM). We discovered that tumor cell invasion into the ECM is profoundly related to cytoskeletal remodeling. We evaluated the drug-screening potential of this model by evaluating five clinically used anti-invasion agents: paclitaxel; cisplatin; irinotecan; oxaliplatin; and gemcitabine. We discovered that gemcitabine inhibited tumor growth, invasion of tumor cells, cytoskeletal remodeling and the ability to invade the ECM, while oxaliplatin principally inhibited invasion. In addition, we also found the model to be very effective for screening for active compounds derived from traditional Chinese medicine, as demonstrated by the natural compound rocaglamide (ROC-A) which inhibited the invasion of tumor cells in a dose-dependent manner at 50 nM. Taken together, our lung cancer-vascular tumor-on-a-chip provides a sound model for studying tumor invasion and demonstrates potential as a platform for precise evaluation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}