Clinical & Experimental Metastasis最新文献

{"title":"PD-1/ PD-l1 Inhibitors and Stereotactic Radiosurgery for Brain Metastases: a systematic review and meta-analysis.","authors":"Yara Alswaiti, Ghena Shahwan, Bakr Alhayek, Sara Absi, Ahmad Alzyoud, Dua'a Kanaan, Badr Nawar, Mohamad Mahmoud Whdan, Enrique Gutierrez-Valencia, Ayah Erjan","doi":"10.1007/s10585-026-10439-5","DOIUrl":"10.1007/s10585-026-10439-5","url":null,"abstract":"<p><strong>Purpose: </strong>Stereotactic radiosurgery (SRS) is the treatment of choice for limited brain metastases (BM), and its combination with PD-1/PD-L1 inhibitors is hypothesized to offer synergistic therapeutic benefits. However, there are concerns regarding augmented risk of radiation-induced brain necrosis (RIBN). This systematic review and meta-analysis evaluate the efficacy and toxicity profile of PD-1/PD-L1 inhibitors combined with SRS or fractionated stereotactic radiotherapy (FSRT).</p><p><strong>Methods: </strong>Four databases were screened, Embase, Web of Science, PubMed and Scopus from inception to November 2025. Primary outcomes were overall survival (OS), extracranial and distant intracranial progression free survival (PFS), and local control (LC). A subgroup analysis was performed based on the primary metastasis origin and radiotherapy treatment modalities. We extracted RIBN events and grade ≥ 3 neurological events. A single-arm meta-analysis was performed using the random-effects modeling. This review protocol was registered on November 2025 on PROSPERO (ID CRD420251171879).</p><p><strong>Results: </strong>Thirty-four studies were included, published between 2016 and 2025 comprising 2,587 patients with BM. The pooled one-year OS was 65% (95% CI 60-69). Patients with BM from Non-Small Cell Lung Cancer (NSCLC) had one-year OS (68%) while melanoma BM had OS (61%). LC and distant intracranial PFS at one year were 87% (95% CI 79-92) and 40.23% (95% CI 17.99-62.47), respectively. The cumulative incidence (CI) of grade 3 RIBN was 5% (95% CI 3-8), and grade ≥ 3 neurological events occurred in 7% (95% CI 4-13). No statistically significant difference in RIBN rates was found between melanoma and NSCLC primaries subgroup.</p><p><strong>Conclusion: </strong>The combination of SRS/FSRT with PD-1/PD-L1 inhibitors is associated with favorable intracranial PFS and LC and a tolerable toxicity profile, with relatively lower rates of grade 3 RIBN. These findings support the feasibility of this combined modality in the immunotherapy era. However, definitive conclusions regarding the incremental risk of RIBN require future prospective trials.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THINKERS-X: multisequence MRI radiomics in a mixture-of-experts model for outcome prediction and exploratory dose-scenario evaluation in lung cancer brain metastases treated with radiosurgery.","authors":"Jheremy S Reyes, Constantinos G Hadjipanayis, Ajay Niranjan","doi":"10.1007/s10585-026-10443-9","DOIUrl":"https://doi.org/10.1007/s10585-026-10443-9","url":null,"abstract":"<p><p>We developed THINKERS-X: Lung, the eXtended multimodal evolution of THINKERS-Lung, to determine whether multisequence MRI radiomics provides incremental value for lesion-specific outcome prediction and exploratory dose-scenario evaluation after Gamma Knife radiosurgery (GKRS) for lung cancer brain metastases. We performed a retrospective single-center study of 767 patients with 3,728 lung cancer brain metastases treated with GKRS. THINKERS-X preserved the original mixture-of-experts and discrete-time survival architecture while adding a dedicated computational neuroradiology expert. Approximately 2,400 radiomic features per metastasis were extracted from pretreatment FSPGR/T1-weighted postcontrast, T2-weighted, and SWAN MRI. Validation used patient-grouped 5-fold cross-validation and a completely closed patient-grouped internal holdout cohort. In grouped cross-validation, THINKERS-X achieved a mean AUC₁₂ of 0.919 ± 0.021 versus 0.876 for THINKERS-Lung (paired difference, 0.043; 95% CI 0.026-0.061; p < 0.001). In the internal holdout cohort, AUC₁₂ improved from 0.863 to 0.929 (95% CI 0.895-0.958), with a paired difference of 0.066 (95% CI 0.031-0.101; p < 0.001). Mean absolute error decreased from 1.26 to 0.84 months. The calibrated Brier score was 0.039, calibration slope 0.94, and intercept 0.04. Radiomics altered model-derived dose-response profiles in 30.0% of metastases and the model-ranked candidate dose in 23.9%. THINKERS-X improved lesion-specific longitudinal prediction, temporal accuracy, and probabilistic calibration beyond THINKERS-Lung while materially altering exploratory dose-scenario evaluation in a subset of metastases. External multicenter and prospective validation are required before clinical implementation.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brachytherapy-based local radiotherapy improves survival in newly diagnosed metastatic cervical cancer.","authors":"Qing-Xiang Wang, Li-Ying Chen, San-Gang Wu, Juan Zhou","doi":"10.1007/s10585-026-10438-6","DOIUrl":"https://doi.org/10.1007/s10585-026-10438-6","url":null,"abstract":"<p><p>To explore if adding local radiotherapy to systemic treatment could enhance the survival of newly-diagnosed stage IVB cervical cancer (CC) patients and compare the impact of different radiotherapy strategies on survival. We included patients diagnosed from 2004 to 2022. Local radiotherapy strategies included external beam radiotherapy (EBRT) and/or brachytherapy (BT). Multivariable Cox regression models were used to assess the link between treatment modality and survival. A total of 4257 patients were involved, all receiving chemotherapy. There were 1280 (30.1%), 2,089 (49.1%), 759 (17.8%), and 129 (3.0%) patients who received chemotherapy alone, chemotherapy plus EBRT, chemotherapy plus EBRT and BT, and chemotherapy plus BT. Using the chemotherapy plus EBRT and BT group as a reference, those on chemotherapy alone had a higher risk of death (cancer-specific survival [CSS]: hazard ratio [HR] 2.037, P < 0.001; overall survival [OS]: HR of 1.992, P < 0.001). Similarly, chemotherapy plus EBRT patients also had an increased risk (CSS: HR 1.576, P < 0.001; OS: HR 1.582, P < 0.001). However, there were no significant differences in CSS (HR 1.082, P = 0.504) and OS (HR 1.083, P = 0.476) between the chemotherapy plus BT group and the reference group. Sensitivity analyses indicated that chemotherapy plus BT and chemotherapy plus EBRT and BT improved survival across subgroups. Our study reveals that adding any form of radiotherapy to chemotherapy for stage IVB CC patients improves survival. BT, alone or combined with EBRT, offers the best outcomes, while EBRT alone has a limited advantage over chemotherapy alone. BT-based local treatment may serve as an effective local treatment option for stage IVB CC.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical resection versus stereotactic body radiotherapy for oligometastatic breast cancer to the liver.","authors":"Lianjie Niu, Lixu Zhu, Qiang Zhang, Yongtao Bai, Qigen Fang, Xianfu Sun, Wenzhi Guo","doi":"10.1007/s10585-026-10436-8","DOIUrl":"10.1007/s10585-026-10436-8","url":null,"abstract":"<p><p>Comparative evidence for hepatic resection and stereotactic body radiotherapy (SBRT) in breast cancer liver oligometastases remains limited. We compared survival, progression, and recovery after these treatments. This three-center retrospective study included adults with breast cancer and ≤ 3 liver metastases undergoing hepatic resection or SBRT between 2010 and 2023. Patients with uncontrolled extrahepatic disease were excluded. Propensity score matching generated 1:1 treatment pairs. Overall survival (OS) was the primary endpoint. Adjusted Cox models evaluated OS and progression-free survival (PFS); progression outcomes were analyzed with death as a competing event. Among 1,055 eligible patients, 708 were matched (354 per group). During a median follow-up of 54.8 months, 432 deaths occurred. Median OS was 48.3 months after surgery and 38.8 months after SBRT (adjusted hazard ratio [HR] for SBRT versus surgery, 1.24; 95% confidence interval [CI], 1.02-1.50). Median PFS was 21.8 and 19.7 months, respectively (adjusted HR, 1.13; 95% CI, 0.96-1.33). The 24 month cumulative incidence of treated-site local failure was 7.1% versus 6.5% (adjusted subdistribution HR, 1.12; 95% CI, 0.75-1.68). Median hospital stay was 8 versus 1 day; among patients restarting systemic therapy, median restart intervals were 45 versus 18 days. The OS association became less precise in analyses restricted to R0 resection or liver-only disease. Resection was associated with longer OS, while SBRT was associated with shorter hospitalization and treatment interruption. Uncertain differences in PFS and local failure do not establish equivalence. Residual confounding and treatment heterogeneity limit causal interpretation and warrant prospective comparative evaluation.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of local ablative therapy combined with first-line tyrosine kinase inhibitors in epidermal growth factor receptor-mutated oligometastatic non-small cell lung cancer: a systematic review and meta-analysis.","authors":"Rahul Bisht, Arusha Desai, Anjali Bhardwaj, Esteban Marcelo Mogrovejo Carrión, Sidharth Misra, Andela Malaj","doi":"10.1007/s10585-026-10437-7","DOIUrl":"10.1007/s10585-026-10437-7","url":null,"abstract":"<p><p>Epidermal Growth Factor Receptor (EGFR) mutations are a significant driver of NSCLC. Although EGFR-Tyrosine Kinase Inhibitors (TKIs) improve outcomes, the development of resistance limits the survival advantages. Local Ablative Therapy (LAT), particularly radiotherapy, may further enhance outcomes in oligometastatic NSCLC, but its benefit remains uncertain. This meta-analysis evaluates the efficacy of LAT with TKI vs. TKI alone. We systematically searched PubMed, Embase, Web of Science, and Cochrane from inception to May 2025 for studies comparing TKI + LAT versus TKI alone, in patients with EGFR-mutated oligometastatic NSCLC. PRISMA guidelines were followed. Outcomes included overall survival (OS), progression-free survival (PFS), and treatment related adverse effects. We pooled hazard ratios (HR) and risk ratios (RR) with a 95% confidence interval (CI) using a random effects model. Statistical Analysis was performed using R software (version 4.4.2). We included 9 studies with 1077 patients, of whom 525 (48.7%) belonged to the TKI + LAT group. Mean follow-up duration was 29.3 months. Patients receiving TKI + LAT had a significantly longer OS (HR 0.50; 95% CI 0.42-0.59; p < 0.001) and PFS (HR 0.44; 95% CI 0.34-0.58; p < 0.001) versus TKI alone. The toxicity risk was not statistically different between the arms, suggesting that LAT did not significantly increase adverse effects. LAT combined with TKI is associated with improved survival in selected patients with EGFR-mutated oligometastatic NSCLC, particularly when delivered as consolidation therapy, with an acceptable safety profile.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles and immune-glial remodeling in lung cancer brain metastasis: potential intersections with exercise-related myokines.","authors":"Zi-Hao Li, Lei Wang, Zhong-Rui Li","doi":"10.1007/s10585-026-10442-w","DOIUrl":"https://doi.org/10.1007/s10585-026-10442-w","url":null,"abstract":"<p><p>Lung cancer brain metastasis develops through reciprocal interactions between metastatic tumor cells and a brain-specific vascular, glial, and immune microenvironment. Tumor-derived extracellular vesicles (EVs) can participate in this process by altering blood-brain barrier (BBB) properties, influencing brain-directed distribution, and transferring regulatory cargo to endothelial and myeloid recipient cells. This review integrates direct evidence from non-small cell lung cancer (NSCLC) brain or central nervous system metastasis with related lung cancer EV studies, while distinguishing these findings from cross-cancer mechanistic evidence. We first describe the transition from the BBB to the heterogeneous blood-tumor barrier and distinguish the contributions of astrocytes, resident microglia, recruited monocyte-derived macrophages, and T cells. We then examine how defined EV cargo, including lnc-MMP2-2, LINC00482, miR-21, L1CAM, and miR-374a-5p, affects barrier integrity, myeloid state, or brain-metastatic behavior. Myeloid responses are interpreted according to cellular origin and function rather than by a fixed M1/M2 binary. Exercise-related myokines and exerkines are considered separately as a hypothesis-generating systemic layer that could influence tumor-cell EV production, deliver signals through muscle-derived EVs, or alter recipient-cell responsiveness; none of these routes has yet been established as a causal mechanism in lung cancer brain metastasis. Together, current evidence supports a role for EV-mediated vascular and immune/glial communication in lung cancer brain metastasis, while leaving the contribution of exercise-related signals unresolved.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of colorectal cancer liver metastases with pure desmoplastic versus non-pure desmoplastic histopathological growth patterns using a targeted gene expression panel.","authors":"Felix Keil, Andreas Lösch, Marco Mühlbauer, Tobias Pukrop, Raquel Blazquez, Hans Jürgen Schlitt, Karolina Müller, Maria Steiger, Yanren Linda Hu, Julia Maurer, Cathleen Brese, Michael Gerken, Matthias Evert, Daniela Hirsch, Rainer Spang, Stefan M Brunner, Katja Evert","doi":"10.1007/s10585-026-10433-x","DOIUrl":"10.1007/s10585-026-10433-x","url":null,"abstract":"<p><p>The histological growth pattern (HGP) at the interface of colorectal adenocarcinoma liver metastases (CRCLM) and liver parenchyma provides important prognostic information. This study aimed to identify transcriptomic signatures underlying the predominant HGPs in CRCLM. We retrospectively evaluated the HGP of 495 CRCLM of 232 patients with metastasectomy at the University Hospital Regensburg between 2003 and 2016. A representative subset of 106 metastases from 53 patients was analyzed for RNA expression at the metastasis-liver interface using the NanoString nCounter® PanCancer Progression Panel. The most common HGPs in the NanoString subcohort were the infiltrative replacement (rHGP, 47.2%) and the non-infiltrative desmoplastic type (dHGP, 46.3%). Unsupervised clustering of CRCLM gene expression profiles identified four gene clusters, two significantly enriched for pure dHGP or pure rHGP. Differential expression analysis between pure dHGP and all other HGPs (i.e., non-pure dHGP) identified 55 significantly differentially expressed genes. Gene set enrichment analysis corroborated previously reported signals (extracellular matrix organization, stromal/endothelial gene sets, and epithelial-mesenchymal transition enrichment in pure dHGP; glucose metabolism in non-pure dHGP) and additionally revealed α6β4 integrin signaling as feature of non-pure dHGP. Patient identity, rather than HGP, was the dominant driver of gene expression variance, though AGR2 was consistently and significantly overexpressed in non-pure dHGP across different analytical strategies. These findings corroborate known transcriptomic differences between HGPs, identify α6β4 integrin signaling as an additional candidate pathway enriched in non-pure dHGP CRCLM, and underscore the substantial contribution of patient-specific factors to gene expression variability in CRCLM outweighing HGP.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic body radiotherapy versus conventional external beam radiotherapy for bone metastases: a meta-analysis.","authors":"Marc Boutros, Jean-Pierre Saad, Guy Awad, Kamal Bou Hamdan, William Eward","doi":"10.1007/s10585-026-10435-9","DOIUrl":"10.1007/s10585-026-10435-9","url":null,"abstract":"<p><p>Stereotactic body radiotherapy (SBRT) and conventional external beam radiotherapy (cEBRT) are widely used treatment options for the management of painful bone metastases. Randomized phase III trials have provided direct comparative evidence for SBRT and cEBRT; however, their results vary according to treatment regimen and clinical endpoint, supporting a broader quantitative synthesis of pain response, local control, retreatment, and safety outcomes. A systematic search was conducted in PubMed, Scopus, the Cochrane Library, and Google Scholar from database inception through January 2026. Comparative clinical studies evaluating SBRT versus cEBRT for bone metastases were included. Outcomes assessed encompassed pain-related measures (change in Visual Analog Scale scores at 3 and 6 months; complete, partial, stable, and progressive pain response), opioid consumption at 3 and 6 months, radiologic local progression or treatment failure at 8 months, re-irradiation at 12 months, skeletal-related events (vertebral and non-vertebral compression fractures), spinal cord compression, treatment-related toxicity, and overall survival at 1 year. Pooled analyses were performed using random-effects models. Early pain reduction at 3 months, partial and stable pain response, and opioid consumption at 3 and 6 months were comparable between SBRT and cEBRT (all p > 0.05). However, SBRT demonstrated superior mid-term outcomes, with a significantly higher complete pain response at 6 months (RR = 1.43; p = 0.001) and a significantly lower rate of progressive pain response at 6 months (RR = 0.61; p = 0.03). SBRT was also associated with markedly improved local disease control, reflected by lower rates of radiologic local progression or treatment failure at 8 months (RR = 0.36; p < 0.001) and a substantially reduced need for re-irradiation at 12 months (RR = 0.13; p < 0.001). Rates of vertebral and non-vertebral compression fractures, spinal cord compression, treatment-related toxicity, and overall survival at 1 year did not differ significantly between treatment modalities. This meta-analysis demonstrates that both SBRT and cEBRT are safe and effective treatment options for patients with painful bone metastases. While early pain palliation and safety outcomes are comparable, SBRT provides superior durability of pain control, reduced pain progression, improved local tumor control, and a markedly lower need for re-irradiation. SBRT may be particularly advantageous for patients with longer expected survival, oligometastatic disease, or lesions at higher risk of progression, whereas cEBRT remains an effective and accessible option for rapid symptom palliation in patients with limited prognosis.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-mediated organotropism in breast cancer metastasis: bridging the gap between molecular mechanisms and clinical application.","authors":"Danil A Pegushin, Marine V Oganesyan, Vladimir N Nikolenko","doi":"10.1007/s10585-026-10432-y","DOIUrl":"10.1007/s10585-026-10432-y","url":null,"abstract":"<p><p>Breast cancer (BC) is characterised by multiple metastasis to various organs and remains a leading contributor to the approximately 10 million annual cancer-related deaths worldwide. The choice of organ for a metastatic site is not random and follows the principle of organotropism. This review develops the concept that exosomes-small extracellular vesicles 30-150 nm in diameter-play a substantial role in forming the pre-metastatic niche by selectively reprogramming target cells and tissues, thereby preparing the organ for the arrival of tumour cells. We examine in detail the molecular mechanisms whereby exosome-contained microRNAs, annexins, tetraspanins and other components drive osteolysis of bone tissue, increase the permeability of the blood-brain barrier (brain metastases arise in roughly 25-27% of triple-negative and 11-20% of HER2-positive BC), and induce fibro-inflammatory changes in the lungs and liver. Particular attention is given to the translational potential of exosomes as diagnostic markers-recent exosome-based classifiers reach a diagnostic accuracy of about 90%-and as agents of targeted therapy. Through a structured comparison of more than twenty primary studies, we provide a critical analysis of the methodological heterogeneity of exosome research and of the status of current clinical trials (8 of 13 catalogued BC trials are purely observational). On this basis, the review outlines concrete, source-supported ways to overcome the existing barriers on the path \"from the bench to the bedside\".</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional activation of EPHB1 by SOX2 promotes epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma.","authors":"Jiaxi Li, Yifan Shi, Sheng Ju, Dong Jiang, Hao Wu, Ji Wu, Haitao Ma","doi":"10.1007/s10585-026-10434-w","DOIUrl":"10.1007/s10585-026-10434-w","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with an unfavorable prognosis, and the molecular mechanisms underlying its metastatic progression remain incompletely defined. Here, we investigated the functional role of ephrin type-B receptor 1 (EPHB1), a member of the ephrin receptor family, in ESCC metastasis. Integrated analyses of RNA-sequencing data and publicly available databases demonstrated that EPHB1 expression is significantly upregulated in ESCC tissues and is positively associated with advanced tumor grade and poor patient survival. Gain- and loss-of-function assays revealed that EPHB1 knockdown markedly inhibited ESCC cell migration, invasion, and epithelial-mesenchymal transition (EMT), whereas EPHB1 overexpression exerted the opposite effects. Consistently, in vivo metastasis assays further confirmed that EPHB1 promotes lung metastasis of ESCC cells. Mechanistically, we identified SRY-box transcription factor 2 (SOX2) as a critical upstream regulator that directly binds to the EPHB1 promoter and transcriptionally activates its expression. Rescue experiments demonstrated that SOX2-induced EMT and invasive capacity are largely mediated through EPHB1. Collectively, these findings uncover a previously unrecognized SOX2/EPHB1 signaling axis that drives ESCC metastasis and suggest EPHB1 as a potential therapeutic target for ESCC.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}