Molecular Oncology最新文献

{"title":"Preoperative circulating tumor cells integrated with imaging analysis for prognostic evaluation in head and neck squamous cell carcinoma.","authors":"Susanne Flach, Gizem Abaci, Tom Huberty, Axel Lechner, Lukas Käsmann, Jens Ricke, Sophia Stöcklein, Martin Canis, Philipp Baumeister, Marianna Alunni-Fabbroni","doi":"10.1002/1878-0261.70299","DOIUrl":"10.1002/1878-0261.70299","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is associated with high locoregional recurrence and poor survival despite multimodal treatment. Reliable biomarkers to guide personalized therapy remain lacking. Circulating tumor cells (CTCs) represent a promising tool, but their clinical utility in HNSCC is insufficiently defined. In this cohort study, 30 stage I-IVb HNSCC patients undergoing curative-intent surgery were enrolled. Preoperative blood samples were analyzed using the FDA-approved CellSearch™ system for CTC count and Programmed death-ligand 1 (PD-L1) expression. Prognostic associations were assessed using Kaplan-Meier analysis and Cox regression. Combined risk models integrating CTC status with radiological features were explored. CTCs were detected in 37.9% (11/29) of patients. CTC positivity was significantly associated with reduced overall survival (P = 0.031). Univariate and bootstrap-adjusted Cox regression identified CTC presence and tumor volume as factors associated with overall survival. Integrating CTC status with tumor volume or nodal stage improved patient stratification, identifying a high-risk group with shorter recurrence-free and overall survival. Preoperative CTC detection may serve as a prognostic biomarker in HNSCC and enhances risk stratification when combined with imaging-derived tumor characteristics, supporting liquid biopsy integration into pre-surgical evaluation.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382370","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 to \"Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors\".","authors":"","doi":"10.1002/1878-0261.70270","DOIUrl":"10.1002/1878-0261.70270","url":null,"abstract":"","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1889"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973880","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":"Dual PI3K/AKT and CDK4/6 inhibition reveals selective sensitivity in an SHH medulloblastoma stem cell model.","authors":"Monika Lukoseviciute, Madeleine Birgersson, Paolo Ceriani, Margareta Wilhelm, Ourania N Kostopoulou","doi":"10.1002/1878-0261.70230","DOIUrl":"10.1002/1878-0261.70230","url":null,"abstract":"<p><p>Medulloblastoma (MB) is a brain tumor for which current treatments cause serious side effects and are not curative for all patients, highlighting the need for more effective and brain-protecting therapies. Recently, we combined phosphoinositide 3-kinase (PI3K) inhibitor (BYL719), fibroblast growth factor receptor (FGFR) inhibitor (JNJ-42756493) and cyclin-dependent kinase (CDK)4/6 inhibitor (PD-0332991) in MB cell lines, and discovered synergistic effects. In the current study, we investigate the most efficient therapies in a normal/tumorigenic neural stem cell model. A sonic hedgehog (SHH)-MB model, including a Gorlin syndrome patient neuroepithelial stem cell line (NES) and its tumor derivative (tNES), was used to evaluate single and combined treatments of PI3K, AKT, FGFR, and CDK4/6 inhibitors (BYL719, AZD5363, JNJ-42756493, and PD-0332991, respectively). Effects on viability, cell confluence and apoptosis were tested on NES and tNES cells cultured as 2D monolayers and 3D spheroids. We found that 2D tNES cells were generally more sensitive to the inhibitory effects of both single and combination treatments compared to 2D NES cells. In the 3D setting, all single drugs were more effective against tNES than NES, except for JNJ-42756493, which showed the opposite trend. Drug combinations in 3D cultures generally resulted in synergistic or additive effects on cell viability in NES and tNES. This study illustrates that single and combined administrations of PI3K, FGFR, CDK4/6, and AKT inhibitors in a NES/tNES model have dose-dependent and additive/synergistic anti-MB activity impacting tumor growth. Their effects on tNES cells were generally more pronounced than on NES; however, the difference in proliferative capacity between the cells should be considered.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1800-1813"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284590","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":"Patient therapy outcome modeling in cancer organoids is improved by cancer-associated fibroblasts and organoid assembly convolution.","authors":"Marcin Grochowski, Liudmyla Dolinchuk, Michał Jerzak, Albert Gandurski, Tomasz Grochowski, Weronika Wojtyś, Maciej Zadrożny, Wojciech Kaźmierczak, Małgorzata Lenarcik, Marta Matejak-Górska, Radosław Samsel, Tomasz Olesiński, Dawid Walerych","doi":"10.1002/1878-0261.70282","DOIUrl":"10.1002/1878-0261.70282","url":null,"abstract":"<p><p>Patient-derived organoids (PDOs) are becoming established as preclinical models for predicting therapeutic responses in cancer, yet their clinical accuracy remains limited by the insufficient representation of the tumor microenvironment and a reliance on static viability readouts. Here, we utilized a living biobank of 30 histopathologically and genetically characterized PDOs, alongside a microenvironment-derived from pancreatic, colon, and gastric cancers, to systematically evaluate their ability to respond to standard-of-care or experimental therapies and model patient outcomes. We assessed the impact of incorporating tissue-matched cancer-associated fibroblasts (CAFs) on treatment responses, finding that their presence not only increased chemoresistance in viability assays but significantly improved patient outcome prediction. To further enhance this predictive accuracy, we developed the Organoid Convolution Assay (OCA), a live-cell imaging-based approach that quantitatively captures dynamics of cell migration, clustering, and assembly during organoid formation. Mathematical modeling of these parameters enabled the significant stratification of donor tumors by stage (T0-T2 vs. T3-T4) and the prediction of patient clinical outcomes. Together, our findings demonstrate that incorporating either tumor microenvironment components or dynamic organoid assembly metrics improves the clinical relevance of PDO-based models.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1694-1712"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163619","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":"EXPRESSION OF CONCERN: DIMP53-1: A Novel Small-Molecule Dual Inhibitor of p53-MDM2/X Interactions with Multifunctional p53-Dependent Anticancer Properties.","authors":"","doi":"10.1002/1878-0261.70284","DOIUrl":"10.1002/1878-0261.70284","url":null,"abstract":"","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1891"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150462","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":"Network divergence analysis identifies adaptive gene modules and two orthogonal vulnerability axes in pancreatic cancer.","authors":"Brian Nelson, Lyanne Delgado-Coka, Natalia Marchenko, Luisa F Escobar-Hoyos, Kenneth R Shroyer, Alisa Yurovsky, Trey Ideker, Gábor Balázsi, Thomas MacCarthy, Scott Powers","doi":"10.1002/1878-0261.70218","DOIUrl":"10.1002/1878-0261.70218","url":null,"abstract":"<p><p>Transcriptional heterogeneity in pancreatic ductal adenocarcinoma (PDAC) arises not only from changes in gene expression but also from dynamic rewiring of gene-gene coordination. Using a divergent-edge framework applied to 77 155 malignant cells from 42 tumors, we identified four reproducible adaptive modules-integrated growth-energy (IGE), stress-adaptive transcription (SAT), IL-2-linked immune evasion (IL2), and multi-pathway collective invasion (MPC)-that cut across canonical PDAC states and reflect distinct regulatory programs. Integrating these modules with CRISPR-Cas9 dependency profiles and PRISM drug-response data revealed that adaptive behaviors collapse into two higher-order axes: a biosynthetic-metabolic IGE axis enriched for translational and DNA-repair dependencies, and a broader SAT-IL2-MPC stress-immune-invasion axis characterized by proteostasis, cytokine-linked, and cytoskeletal vulnerabilities. This architecture emerges only when divergent-edge modules are mapped into functional genomics space. Module activity also carried clinical relevance in PDAC. SAT-high tumors showed poorer survival, while MPC-high tumors exhibited a similar adverse trend; together, these modules defined a stress-immune-invasion poor-prognosis axis. In contrast, IGE activity showed no overall risk association, although an optimal-cut point-defined IGE-high subgroup displayed modestly improved survival.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1857-1876"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326764","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":"Subtype-specific enhancer RNAs define transcriptional regulators and prognosis in breast cancers.","authors":"Aamena Y Patel, Peyman Zarrineh, Nathnael T Tuffa, Jigar H Sheth, Sumitra Mohan, Mudassar Iqbal, Sankari Nagarajan","doi":"10.1002/1878-0261.70214","DOIUrl":"10.1002/1878-0261.70214","url":null,"abstract":"<p><p>Gene expression is tightly controlled by DNA elements called enhancers by associating with lineage-specific transcription factors. These enhancers transcribe noncoding RNAs (called enhancer RNAs or eRNAs). eRNA expression is an early indicator of transcription factor activity and is associated with treatment response and survival in cancer patients. By analysing ~ 300 000 eRNA loci profiled using RNA-sequencing data sets from 975 breast cancer patients using machine learning approaches, we categorised eRNAs specific to breast cancer molecular subtypes and survival. We associated these eRNAs with subtype-specific mRNAs to define proximal co-expressed regulatory eRNAs (ProxCReAm), which are enriched in pathways characteristic of their respective subtypes. Interestingly, cistrome and transcription factor motif analyses on these eRNAs highlighted involvement of diverse nuclear receptors (GR/AHR for luminal and GR/RAR for basal) and FOX factors in luminal regions. Moreover, luminal eRNAs were associated with better outcomes and Her2 eRNAs with worse outcomes in patients. Overall, we demonstrate that machine learning approaches performed on RNA-seq data sets can classify functionally relevant subtype-specific and prognostic eRNAs, which can identify critical gene pathways and transcription factor networks in breast cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1835-1856"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326730","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":"TRAIL-PEG-Apt-PLGA nanosystem as an aptamer-targeted drug delivery system potential for triple-negative breast cancer therapy using in vivo mouse model.","authors":"Gulen Melike Demirbolat, Aslihan Kucuk, Omer Erdogan, Samed Ozer, Bensu Kozan, Tugba Cuceli, Erkan Gumus, Evrim Cevik, Ozge Cevik","doi":"10.1002/1878-0261.70202","DOIUrl":"10.1002/1878-0261.70202","url":null,"abstract":"<p><p>Targeted drug therapy is very important for the treatment of triple-negative breast cancer (TNBC), and the development of carrier systems to deliver apoptosis-inducing proteins such as TRAIL to cells is important in cancer therapy. In this study, a nanosystem formulation (TRAIL-PEG-Apt-PLGA) encapsulating TNBC-targeted aptamer-bound-TRAIL protein was performed and the efficacy of this system was evaluated in a mouse tumor model. The characterization of TRAIL-PEG-Apt-PLGA was confirmed by FTIR, NTA and SEM microscopy. The efficacy of TRAIL-PEG-Apt-PLGA was evaluated by in vitro release assays and interactions with TNBC cells (MDA-MB-231) and healthy breast cells (MCF-10A). TRAIL-PEG-Apt-PLGA was administered intravenously to NOD/SCID gamma mouse breast tumors and evaluated in vivo. Pharmacokinetics, bioavailability testing, histological staining (DR4/DR5, TUNEL, HE staining) and molecular alterations with PCR array were evaluated in tumor tissues. TRAIL-PEG-Apt-PLGA induced apoptosis in both in vivo and in vitro studies. It was found that it regulated cellular responses along with apoptotic mechanisms in cells without developing resistance in suppressing tumor growth by making changes on Atf2, Casp8, Bcl2 and Irf5 genes and proteins. As a result, the biotechnological drug potential of TRAIL was discovered in an aptamer-bound nanosystem for the treatment of triple-negative breast cancer and innovative applications for clinical use.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1742-1761"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142933","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":"Deciphering transcriptional plasticity in pancreatic ductal adenocarcinoma reveals alterations in sensory neuron innervation.","authors":"Elena Genova, Michele Montrone, Uday Rangaswamy, Francesco Diversi, Irene Schiavo, Denise Ferrarini, Roberta Di Florio, Irene Longo, Michele Coscia, Nicola Zamboni, Giorgia Demontis, Lisa Veghini, Vincenzo Corbo, Remo Sanges, Paul Heppenstall","doi":"10.1002/1878-0261.70233","DOIUrl":"10.1002/1878-0261.70233","url":null,"abstract":"<p><p>Neuronal innervation of the pancreas has historically been characterized using marker-based classification and physiological studies, but its transcriptomic landscape remains only partially explored. A detailed molecular profile of pancreatic sensory neurons could provide insights into their role in health and disease, particularly in pancreatic ductal adenocarcinoma (PDAC), where neural remodeling influences tumor progression and pain signaling. Wild-type and PDAC mice were injected with the retrotracer Fast Blue into pancreatic or cancerous tissue. Dorsal root ganglia were dissociated, and Fast Blue-positive sensory neurons were isolated, lysed, and analyzed using single-cell RNA sequencing. Data were validated using immunofluorescence, organoid cultures and qPCR. We performed transcriptomic profiling of sensory neurons innervating the pancreatic head and tail under normal and cancer conditions. Our analysis identified neurofilament-containing neurons as the predominant sensory subtype in both contexts, while non-peptidergic neurons were underrepresented in tumor-associated innervation. Differential gene expression analysis revealed a unique subset of genes upregulated in sensory neurons innervating pancreatic tumors, many linked to mitochondrial activity. Further validation also revealed the presence of transcripts transferred via extracellular vesicles (including the Pdx1-CreERT2 transgene from the KPC mouse model), suggesting a novel mechanism of tumor-neuron interaction. Our findings provide a detailed characterization of pancreatic and pancreatic ductal adenocarcinoma sensory innervation. We identified tumor-derived RNA within sensory neurons in the PDAC mouse model, suggesting an extracellular vesicle-mediated RNA transfer mechanism that may remodel sensory signaling and open new prospects for diagnostic and therapeutic innovation in PDAC. Impact statement Transcriptomic profiling of pancreatic sensory neurons reveals shifts in neuronal populations, tumor-specific mitochondrial gene upregulation, and potential extracellular vesicle-mediated transcript transfer. Circulating tumor transcripts in KPC mice provide a reference for pancreatic innervation, tumor-nerve interactions, and therapeutic targets.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1726-1741"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473902","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: Mechanism of p27 Upregulation Induced by Downregulation of Cathepsin B and Upar in Glioma.","authors":"","doi":"10.1002/1878-0261.70288","DOIUrl":"10.1002/1878-0261.70288","url":null,"abstract":"<p><strong>Retraction: </strong>S. Gopinath, K. Alapati, R. R. Malla, C. S. Gondi, S. Mohanam, D. H. Dinh, and J. S. Rao, \"Mechanism of p27 Upregulation Induced by Downregulation of Cathepsin B and Upar in Glioma,\" Molecular Oncology 5, no. 5 (2011): 426-437, https://doi.org/10.1016/j.molonc.2011.07.004. The above article, published online on 26 July 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Kevin Ryan; the Federation of European Biochemical Societies; and John Wiley and Sons Ltd. Following publication, concerns were raised by a third party regarding the duplications of image elements Figure 7, as well as duplicated western blot bands between Figures 4C and 6B, between Figures 1C and 4C, within Figure 3A and within Figure 6A. Internal investigation confirmed the duplications in these figures and additionally identified undeclared splice marks within Figures 2D and 4C, duplicated western blot bands between Figure 3A and Figure 4A of a previous publication with shared authors (DOI: 10.1371/journal.pone.0011668) where the same bands were presented in a different scientific context. The retraction has been agreed because the concerns were determined to affect the authenticity and reliability of the data and results presented. The authors have been informed of the retraction decision where possible; however, current contact details could not be verified.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1892"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199283","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}