Cancer Cell International最新文献

{"title":"Indole analogs and the aryl sulfonamide AqB011 potently restrain the invasiveness of glioblastoma cells, as determined in ex vivo xenograft tissue slice co-cultures (XTCCs).","authors":"Kim K Wagner, Andrea J Yool, Rohan A Davis, Katrin Becker, Heike Franke, Achim Aigner","doi":"10.1186/s12935-026-04489-8","DOIUrl":"10.1186/s12935-026-04489-8","url":null,"abstract":"<p><strong>Background: </strong>Glioblastomas (GBMs) are highly invasive and heterogeneous in nature which strongly contributes to poor survival of patients, averaging 15 months after diagnosis. With little treatment options being available in particular for addressing GBM invasiveness, there is a high need for supplementary therapies in addition to classical cytostatics like Temozolomide (TMZ).</p><p><strong>Methods: </strong>The aim of this study was to examine promising compounds, the natural indole scaffold RAD114 and three semisynthetic analogs (RAD118, RAD119, RAD120) as well as the aryl sulfonamide AqB011, for their inhibitory potential specifically on tumor cell invasion. For this, GBM xenograft tissue slice tandem co-culture (XTCC) models were employed, closely reflecting the in vivo patient situation. In particular, these ex vivo tissue slice air-liquid interface (ALI) models also allow for distinguishing between inhibitory effects on bulk tumor growth vs tumor cell invasion into the normal brain tissue.</p><p><strong>Results: </strong>Profound anti-invasive effects of the natural indole scaffold RAD114, three semisynthetic analogs (RAD118, RAD119, RAD120), and the aryl sulfonamide AqB011 were observed in XTCC models based on G55T2 and U87-MG GBM xenografts co-cultured with mouse brain slices in ALI tandem co-culture. While effects on bulk tumor growth were rather moderate, profound inhibition or even abolishment of tumor invasion was observed, dependent on the compound, its dosage and the model. At a non-toxic concentration (10 µM), RAD118 and AqB011 showed the highest effectiveness in reducing tumor invasion. Combination effects at sub-optimal compound dosages were observed as well.</p><p><strong>Conclusions: </strong>Both compound classes - the tested semisynthetic indole analogs and the sulfonamide derivative - may be promising lead candidates for drugs useful to specifically address the issue of GBM invasiveness. They strongly restrained GBM cell invasion, alone and in combination. Rather than acting through cytotoxic effects, they specifically inhibit cell migration into native brain tissue.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149294846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical fusion among non-malignant cells: Unveiling the link between post-fusion-induced genome chaos and cancer initiation.","authors":"Julian Weiler, Grigorios Raphael Topsis, Thomas Dittmar","doi":"10.1186/s12935-026-04466-1","DOIUrl":"10.1186/s12935-026-04466-1","url":null,"abstract":"<p><strong>Background: </strong>Atypical cell fusion events can disrupt the normal post-fusion process, initiating genome chaos through the merging of parental genomes accompanied by severe and complex gross structural changes. Consequently, unscheduled fusion events can accelerate tumorigenesis by fostering persistent genomic instability, serving as catalysts in the post-hybrid selection process and decisively contributing to the acquisition of novel and malignant properties. Understanding how hybrid cells survive after fusion and identifying specific transcriptional and phenotypic signatures that characterize hybrids across different fusion phases may provide valuable insights to counteract the evolution of cancer-initiating hybrids.</p><p><strong>Methods: </strong>Two distinct populations of H2B-fluorescence-labeled M13SV1 breast epithelial cells were cocultured to yield H2B double-fluorescence-tagged hybrid clones derived from spontaneous cell fusion. Hybrid clones were picked and propagated individually to establish early- and late-passage hybrid populations. Hybrid clone and passage-dependent cell fate studies were conducted via live-cell imaging and high-resolution 3D imaging to capture aberrant mitotic outcomes. Hybrids were evaluated for ploidy status, cell cycle DNA damage, cell/nuclear morphology and transcriptomic profiling using a set of distinct methods, including flow cytometry (ploidy/DNA damage analysis), diverse cell metrics and image processing software (cell/nuclear scoring) and RNA sequencing (transcriptome profiling). Subsequently, EMT marker expression, migration/invasion, and colony- and sphere-forming capacities were investigated.</p><p><strong>Results: </strong>Near-tetraploid hybrids undergo a hybrid clone-dependent ploidy reduction process upon long-term passaging, which is associated with cell shrinkage. Ploidy reduction was not coupled with substantial loss of DNA lesions but rather correlated with the degree of nuclear deformation. Hybrids were extremely chromosomally unstable, as evidenced by a high incidence of aberrant mitoses, nuclear pleomorphism, and elevated scores of micro- and multinucleation. Additionally, a subset of hybrids underwent ploidy reversal, characterized by endoreplication, cytokinesis failure or refusion, leading to the formation of exceptionally large or multinucleated cells. Transcriptome analysis revealed a differentially expressed gene profile of the hybrids associated with EMT, migratory aptitude and cancer-related traits, as validated by migration/invasion assays, Western Blots and colony/mammosphere assays.</p><p><strong>Conclusion: </strong>Collectively, the data highlight the catastrophic potential of atypical fusion processes, wherein widespread and large-scale genomic changes can occur at a rapid macroevolutionary pace and potentiate the risk for subclonal heterogeneity and malignancy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Cyclin D3 predicts disease-free survival in breast cancer.","authors":"Yayun Chi, Sheng Huang, Mengying Liu, Liang Guo, Xuxia Shen, Jiong Wu","doi":"10.1186/s12935-026-04480-3","DOIUrl":"10.1186/s12935-026-04480-3","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold atmospheric plasma treated medium (PTM) induce antitumor effects in human ovarian cancer cells.","authors":"Franziska Keßler, Franziska Oelkrug, Ernst Oberlechner, Jürgen Andress, Sara Y Brucker, André Koch, Daniel A Carvajal Berrio, Katja Schenke-Layland, Martin Weiss","doi":"10.1186/s12935-026-04461-6","DOIUrl":"10.1186/s12935-026-04461-6","url":null,"abstract":"<p><p>Plasma treated solutions (PTS) have emerged as a promising anticancer strategy due to their ability to generate reactive oxygen and nitrogen species (RONS) that induce oxidative stress and disrupt multiple cellular pathways. Despite increasing interest in plasma-based cancer therapies, the mechanisms underlying their effects in ovarian cancer remain incompletely understood. This study aimed to investigate the biological effects of plasma treated medium (PTM) in ovarian cancer models, focusing on cell viability, caspase 3/7 activity, DNA damage, cell cycle progression, and mitochondrial metabolism.</p><p><strong>Methods: </strong>Three established ovarian cancer cell lines were treated with PTM to evaluate dose-dependent effects on cell viability using a resazurin assay. Apoptotic signaling was assessed by caspase 3/7 activity assays. DNA damage was analyzed by immunofluorescence staining of γH2AX, while cell cycle alterations were evaluated using propidium iodide staining and flow cytometry. Mitochondrial metabolism was investigated using fluorescence lifetime imaging microscopy together with NADH and FAD autofluorescence imaging. In addition, patient-derived high-grade serous ovarian cancer cells isolated from ascites were analyzed as independent biological replicates to assess biological relevance.</p><p><strong>Results: </strong>PTM induced dose-dependent inhibition of cell viability with IC₅₀ values ranging from 1:4 to 1:1.1 PTM dilutions across the tested cell lines. PTM treatment triggered γH2AX-associated DNA damage, caspase 3/7 activity, and dynamic alterations in cell cycle progression. Fluorescence lifetime imaging revealed significant reductions in free NADH and changes in protein-bound NADH and FAD, consistent with mitochondrial dysfunction. These metabolic alterations were accompanied by morphological changes from filamentous mitochondrial networks to punctate structures. Patient-derived ovarian cancer cells showed partial responses, primarily reflected in cell cycle modulation, highlighting both biological relevance and intercellular heterogeneity.</p><p><strong>Conclusions: </strong>PTM exerts multifactorial anticancer effects in ovarian cancer models by inducing DNA damage, caspase 3/7 activity, cell cycle alterations, and mitochondrial dysfunction. These findings provide further insight into the biological effects of plasma-based cancer therapies and support the potential of plasma treated solutions as a novel therapeutic strategy for ovarian cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: CAR-T and TIL therapies in solid tumors: barriers, clinical lessons, and convergent solutions.","authors":"Duc-Hiep Bach, Van T Hoang, Pham Thi Viet Huong, Dinh Duy Nguyen, Thanh Liem Nguyen","doi":"10.1186/s12935-026-04464-3","DOIUrl":"10.1186/s12935-026-04464-3","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Next-generation CAR-NK cell therapy: engineering strategies, translational challenges, and future perspectives in cancer immunotherapy.","authors":"Minoo Bakhtiari, Hamid Nickho, Mahmoud Mahmoudi, Fahimeh Lavi Arab, Akram Hoseinzadeh, Rasoul Baharlou","doi":"10.1186/s12935-026-04470-5","DOIUrl":"10.1186/s12935-026-04470-5","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced survival through repeated photodynamic therapy and almost complete tumor regression by prior radiation therapy in an orthotopic rat bladder cancer model.","authors":"Mandy Berndt-Paetz, Sandra Nürnberger, Susann Gonsior, Ewelina Pączek-Hippe, Ina Patties, Annett Weimann, Romy Michalik, Jochen Neuhaus, Annegret Glasow","doi":"10.1186/s12935-026-04465-2","DOIUrl":"10.1186/s12935-026-04465-2","url":null,"abstract":"<p><strong>Introduction: </strong>The development of new organ-preserving treatment alternatives is still an important issue in bladder cancer (BCa) research. A combination of minimally-invasive photodynamic therapy (PDT) with ionizing radiation (IR) could be beneficial for bladder tumor regression. Here, we tested the hypothesis that PDT with the near-infrared photosensitizer tetrahydroporphyrin-tetratosylate (THPTS) could treat bladder tumors safely and effectively in an orthotopic rat model.</p><p><strong>Materials and methods: </strong>Response additivity analysis of cytotoxicity was investigated in cultured tumor cells (AY-27) and spheroids consisting of AY-27 and bladder fibroblasts of F344 Fischer rats. For in vivo evaluation, tumors were induced in female Fischer rats by intravesical instillation of AY-27 cells. Triple-time treatments were performed, with ten rats each in four treatment groups: untreated controls (UTC), PDT, IR, PDT with prior IR (IR + PDT). Animals were euthanized when reaching the termination criteria, and bladders were evaluated by macroscopy, histology and CD45 immunohistology.</p><p><strong>Results: </strong>Synergism of combined treatment was demonstrated for all tested THPTS concentrations in AY-27/fibroblast spheroids but not in 2D cultured AY-27 cells. Tumor cell inoculation resulted in massive growth of solid bladder tumors (pT3a/b) in UTC. Triple-time treatment led to doubling of survival in the PDT group (mOS: 70 d) compared to UTC group (mOS: 36.5 d). IR monotherapy and IR + PDT resulted in complete survival without reaching the termination criteria. Histology revealed advantage of combination therapy vs. IR monotherapy by demonstrating treatment responses in all tumors of the IR + PDT group.</p><p><strong>Conclusion: </strong>This is the first in vivo study reporting doubling of survival time after PDT with a new near-infrared photosensitizer, and nearly complete tumor remission by neoadjuvant IR. This multimodal approach possibly allows minmally-invasive, organ-preserving BCa treatment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold atmospheric plasma affects metabolic processes in malignant melanoma.","authors":"Erika Rein, Tom Zimmermann, Stefan Fischer, Zubeir El Ahmad, R Verena Taudte, Arne Gessner, Martin F Fromm, Melanie Kappelmann-Fenzl, Anja Bosserhoff","doi":"10.1186/s12935-026-04448-3","DOIUrl":"10.1186/s12935-026-04448-3","url":null,"abstract":"<p><strong>Background: </strong>Partially ionized gas, also known as cold atmospheric plasma (CAP), is reported to have anti-tumor specific properties via reactive oxygen and nitrogen species (RONS) in different tumor entities. Many CAP effects have already been studied, but the exact influence on metabolism has yet to be defined.</p><p><strong>Methods: </strong>Analyses of metabolic substrates, metabolic pathways, genes, mRNA and nitration were performed to investigate CAP-treated and untreated melanoma and non-malignant cells.</p><p><strong>Results: </strong>We discovered a dose-dependent downregulation of oxidative phosphorylation and glycolysis in CAP-treated compared to untreated melanoma cells, whereas for non-malignant cells we saw no change in the oxidative phosphorylation and even an increase in the glycolysis. Gene set enrichment analyses demonstrated a downregulation of gene sets associated with metabolic processes in melanoma cells. These effects could be explained by posttranslational modification via tyrosine nitration, induced by RONS. A higher induction of protein nitration was found in CAP-treated melanoma cells opposed to non-malignant cells. This difference may contribute to the antitumor-specific effects of CAP.</p><p><strong>Conclusion: </strong>This study shows different molecular and metabolic responses of melanoma and non-malignant cells in vitro. It thereby contributes to a better understanding of the antitumor-specific effects of CAP and facilitates the development of CAP-based treatments.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.","authors":"Qingmiao Shi, Shuwen Yang, Siying Li, Chen Xue","doi":"10.1186/s12935-026-04444-7","DOIUrl":"10.1186/s12935-026-04444-7","url":null,"abstract":"<p><p>Digestive system cancers, including malignancies of the oral cavity, esophagus, stomach, liver, pancreas, and colorectum, rank among the most prevalent tumors worldwide, with persistently high incidence and mortality. Notch signaling is a highly conserved pathway that orchestrates essential cellular processes such as differentiation, proliferation, and development; its dysregulation has been increasingly linked to various diseases, particularly digestive system cancers. Accumulating evidence indicates that aberrant Notch signaling is closely associated with the development of these malignancies, where it influences tumor initiation, progression, metastasis, and therapy resistance. Notably, depending on cellular context, Notch signaling may also exhibit tumor-suppressive effects in certain digestive system cancers. Understanding the role of Notch signaling in these tumors is essential for the development of more effective therapeutic strategies. Currently, multiple preclinical studies are investigating agents targeting the Notch pathway. This review summarizes current evidence on Notch signaling in digestive system cancers and points to open questions that warrant further study to inform future therapeutic strategies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NPTXR as a novel therapeutic target: efficacy of antibody-drug conjugates in preclinical tumor models.","authors":"Mykola Lyndin, Michel Janicot, Justus Müller, Peter Schiemann, Gunther Wennemuth","doi":"10.1186/s12935-026-04438-5","DOIUrl":"10.1186/s12935-026-04438-5","url":null,"abstract":"<p><strong>Background: </strong>The neuronal pentraxin receptor (NPTXR) is mainly expressed in the cytoplasm of a subset of neuronal cells in the cerebral cortex. While NPTXR may be involved in mediating uptake of synaptic material during synapse remodeling or synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses during embryonic development, NPTXR expression has recently been shown to be elevated in tissues from patients with gastric cancer.</p><p><strong>Methods: </strong>NPTXR protein expression was evaluated in human cancer and healthy tissue samples. We then generated antibody-drug conjugates based on YB-800 (YB-800_ADCs), a fully humanized monoclonal antibody selectively targeting NPTXR. The cross-reactivity of YB-800 and YB-800_ADCs were assessed, as well as their tumor inhibitory effects in experimental tumor models.</p><p><strong>Results: </strong>NPTXR protein was highly and consistently expressed in human tissue samples from multiple cancer types but only minimally expressed, if at all, in healthy tissues. Treatment with YB-800_ADCs inhibited tumor cell proliferation/survival in engineered HEK293 cells overexpressing the human NPTXR. YB-800_ADCs were also found to have pronounced anti-tumor effects in mice bearing NPTXR-expressing HEK293 tumors at well-tolerated doses. Initial anti-tumor findings were further confirmed using a naturally occurring NPTXR-expressing human bladder PDX model.</p><p><strong>Conclusions: </strong>NPTXR is an oncofetal protein that is highly expressed in multiple human cancers but minimally expressed in healthy tissues. We have established NPTXR as a new tumor marker and have developed antibody-drug conjugates using YB-800, a novel, first-in-class, humanized monoclonal antibody targeting the human NPTXR. Initial results demonstrate that YB-800_ADCs have pronounced anti-tumor effects in vivo in NPTXR-expressing cancer cells. Continued evaluation of YB-800_ADCs is warranted.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"26 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}