Discover. Oncology最新文献

{"title":"Demethylase ALKBH5 inhibits proliferation and promotes apoptosis of hepatocellular carcinoma cells by decreasing methylation levels and regulating SOCS3/STAT3 signaling.","authors":"Tianhao Wu, Zhen Yang, Jiansheng Chen, Yihao Liu, Dongqi Li, Xue Xing, Qiang Li","doi":"10.1007/s12672-026-05205-8","DOIUrl":"https://doi.org/10.1007/s12672-026-05205-8","url":null,"abstract":"<p><p>In this study, we investigated the role of ALKBH5 in the pathogenesis of hepatocellular carcinoma (HCC), focusing on the underlying molecular mechanisms. Comparative analysis of ALKBH5 expression profiles between hepatocellular carcinoma (HCC) tissues and adjacent non-tumorous liver tissues revealed a significant downregulation of ALKBH5 in malignant tissues. To investigate the functional significance of ALKBH5 in HCC pathogenesis, we employed both gain-of-function and loss-of-function approaches in HCC cell lines, utilizing overexpression and RNA interference strategies. Clinical correlation studies demonstrated that decreased ALKBH5 expression levels were significantly associated with reduced overall survival rates in HCC patients, suggesting its potential role as a prognostic biomarker. Furthermore, upregulation of ALKBH5 expression inhibited HCC cell proliferation and induced apoptosis. Through mechanistic studies, we identified SOCS3 as a downstream target of ALKBH5, which negatively regulates the STAT3 signaling pathway. In conclusion, our findings suggest that ALKBH5, as a demethylase, suppresses HCC cell proliferation and promotes apoptosis by reducing methylation levels and modulating the SOCS3/STAT3 pathway. These insights deepen our understanding of the molecular mechanisms underlying HCC and provide potential avenues for future therapeutic development.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of the tumor microenvironment for prognostication of recurrence in glioma and targeting stemness using an adjuvant.","authors":"Puneet Gandhi, Kavita Peter, Sandeep Sorte, Nitin Garg","doi":"10.1007/s12672-026-05552-6","DOIUrl":"https://doi.org/10.1007/s12672-026-05552-6","url":null,"abstract":"<p><strong>Background: </strong>Cells expressing stemness markers have the potential to convert normal stem cells or cancer cells into cancer stem cells (CSCs), and their overexpression is known to foster tumor progression. They form a dynamic aspect of the tumor micro-environment and are involved in tumor relapse/recurrence and resistance to treatment. The expression of several stemness markers is linked with survival & prognosis of glioma patients. Still, no single marker is recognized to have substantial diagnostic value and the best predictive power for survival and prognosis. Therefore, we undertook an evaluation of the systemic expression of a panel of HMGA1, hTERT, CD117, and PDGFRα as predictors of recurrence in glioma.</p><p><strong>Methods: </strong>The circulating levels of the aforementioned stemness markers were estimated in serum/plasma from n = 15 glioma patients using enzyme-linked immunosorbent assay (ELISA) to establish their values at the time of diagnosis and recurrence. Their expression was corroborated and validated in corresponding glioma tissues by fluorescence-immunohistochemical staining. Kaplan-Meier curves were generated to assess the influence of these markers on overall survival and relapse-free survival. Univariate Cox regression hazards ratio was employed to assess risk factors of adverse outcomes. HMGA1 and hTERT were targeted in vitro in the glioblastoma modelusing 10 µM curcumin to curtail stemness and migration potential.</p><p><strong>Results: </strong>Soluble HMGA1, hTERT, CD117, and PDGFRα were found to be significantly elevated in the pre-treatment glioma group compared to controls (p = 0.034, p = 0.0002, p = 0.0003, and p = 0.024, respectively). The results of tissue expression of the biomarkers were consistent with systemic levels. Paired sample analysis at diagnosis and relapse revealed significantly upregulated systemic hTERT and PDGFRα levels at relapse (p = 0.047 and p = 0.013, respectively). Log-rank analysis and univariate Cox regression hazards ratio presented a higher expression of hTERT and HMGA1 to be significantly correlated with a shorter OS and RFS. Cells targeted with 10 µM curcumin displayed a reduction in hTERT and HMGA1 protein expression at 24 h, along with a decrease in migration potential. The systemic levels of these markers have shown promise as prognostic indicators of recurrence.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-read sequencing enhances molecular and epigenetic characterisation in brain tumour diagnostics.","authors":"Sara Petrin, Špela Kert, Andrej Zupan, Alja Videtič Paska, Katarina Kouter, Alenka Matjašič","doi":"10.1007/s12672-026-05595-9","DOIUrl":"https://doi.org/10.1007/s12672-026-05595-9","url":null,"abstract":"<p><p>Long-read sequencing (LRS) technologies have enhanced molecular diagnostics by enabling comprehensive analysis of genetic, epigenetic and transcriptomic alterations in various genetic diseases and cancer. Emerging applications of LRS in central nervous system (CNS) tumour diagnostics demonstrate its ability to detect clinically relevant mutations, gene fusions, copy number variations, and epigenetic changes. With ongoing advancements in sequencing chemistry and data analysis tools, LRS has the potential to improve the molecular diagnosis and management of CNS tumours ultimately leading to improved patient outcomes. However, despite numerous advantages, several challenges remain, including the need for high-quality nucleic acids and the lack of standardised bioinformatics tools. Integrating LRS into routine diagnostics requires further improvement of computational pipelines and the development of standardised analytical workflows. Our review aims to provide insight into novel applications of LRS in CNS tumour diagnostics and a comprehensive overview of available bioinformatics tools to support the analysis and interpretation of LRS data.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR guided gene knockout in pancreatic ductal adenocarcinoma molecular mechanisms and therapeutic strategies.","authors":"Muhammad Shahid Mehmood, Maida Noor, Somal Meraj, Arbab Hassan, Umad Ali, Mohammad Jalal Nazari","doi":"10.1007/s12672-026-05532-w","DOIUrl":"https://doi.org/10.1007/s12672-026-05532-w","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies worldwide, characterized by late-stage diagnosis, profound chemoresistance, and a five-year survival rate that barely exceeds 12%. The fibrotic stromal barrier surrounding the tumor actively suppresses immune infiltration and blocks drug delivery, rendering conventional treatment options largely ineffective. CRISPR-Cas9-mediated gene knockout represents a promising strategy to overcome this stromal barrier-associated therapeutic resistance by enabling precise disruption of genes that sustain desmoplastic signaling, stromal-immune crosstalk, and drug efflux pathways within the tumor microenvironment. In this context, CRISPR-Cas9-guided gene knockout has opened a new chapter in PDAC research by enabling precise, scalable analysis of the cancer genome. Functional screens using this technology have mapped critical oncogenic dependencies, identifying mutant KRAS, TP53, SMAD4, and CDKN2A as high-value targets, while simultaneously revealing synthetic lethal interactions that were previously inaccessible through pharmacological approaches. These discoveries are now being translated into therapeutic strategies aimed at silencing driver mutations, restoring chemosensitivity, and reprogramming the immunosuppressive tumor microenvironment. Delivery platforms, including lipid nanoparticles, viral vectors, and extracellular vesicles, are being refined to navigate the physical barriers unique to PDAC. Patient-derived organoids and xenograft models are providing the translational framework needed to evaluate these interventions under clinically relevant conditions. This review examines the molecular mechanisms of CRISPR-guided knockout, the genetic vulnerabilities it has uncovered in PDAC, the therapeutic strategies emerging from this work, and the delivery systems supporting clinical translation. The remaining barriers and the steps needed to bring this technology to patients are also discussed.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of genes related to macrophage polarization and mitochondrial dysfunction in hepatocellular carcinoma and prognostic modeling via LASSO-Cox regression.","authors":"Bin-Bin Cheng, Wei-Ping Tu, Xiao-Yu Tu, Bai Li","doi":"10.1007/s12672-026-05546-4","DOIUrl":"https://doi.org/10.1007/s12672-026-05546-4","url":null,"abstract":"<p><strong>Aim: </strong>Hepatocellular carcinoma (HCC) is the most common primary liver cancer in adults, with increasing incidence. It is helpful to establish a prognostic risk prediction model related to macrophage polarization and mitochondrial dysfunction associated with HCC.</p><p><strong>Methods: </strong>Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression, Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) network.</p><p><strong>Results: </strong>A total of 7 model genes (EZH2, G6PD, HMGA2, MAGEB2, PYCR1, SLC7A11, and SPP1) were identified. And the LASSO-Cox model showed preliminary prognostic predictive performance in the TCGA-LIHC cohort (0.9 > AUC > 0.7), with decision curve analysis (DCA) showing clinical potential, particularly in the third year. GSEA revealed that genes associated with Liver hepatocellular carcinoma (LIHC) exhibited enrichment in functions and pathways, notably including FCGR3A Mediated IL10 Synthesis, etc. GSVA indicated multiple pathways were significant in both Low-Risk and High-Risk groups, such as the biocatamcm pathway (p < 0.05). The PPI Network shows connections among G6PD, SLC7A11, HMGA2, and EZH2, with GeneMANIA predicting their interactions with similar function genes.</p><p><strong>Conclusion: </strong>Our study screened candidate prognostic genes associated with macrophage polarization and mitochondrial dysfunction based on bioinformatics analysis and established a prognostic model.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glomangiopericytoma of the nasopharynx in a previously irradiated field mimicking recurrent nasopharyngeal carcinoma.","authors":"Jinzhi Wu, Shasha Shen, Mingna Wu, Guangyong Feng, Xiaoxia Gou","doi":"10.1007/s12672-026-05591-z","DOIUrl":"https://doi.org/10.1007/s12672-026-05591-z","url":null,"abstract":"<p><strong>Background: </strong>Glomangiopericytoma (GPC) is a rare sinonasal mesenchymal neoplasm with distinctive morphologic and molecular features, most commonly arising in the nasal cavity and paranasal sinuses. Occurrence in the nasopharynx is exceptionally uncommon and may create a substantial diagnostic challenge, particularly in long-term survivors of nasopharyngeal carcinoma (NPC) after radiotherapy, in whom a newly detected nasopharyngeal mass is often clinically presumed to represent recurrent carcinoma.In this setting, diagnosis should rest on the combined assessment of growth architecture, cytologic blandness, and a targeted exclusionary immunohistochemical panel rather than on clinical history, imaging appearance, or any single marker alone.</p><p><strong>Case presentation: </strong>A man in his early seventies, previously treated with chemoradiotherapy for NPC approximately 30 years earlier, presented with a 15-day history of right-sided ptosis and headache. Nasoendoscopy demonstrated a smooth, highly vascular mass arising from the right posterior nasopharyngeal wall. Magnetic resonance imaging revealed a skull-base lesion extending toward the cavernous sinus, with radiologically suspicious cervical lymphadenopathy that was not pathologically sampled, raising concern for recurrent malignancy. Endoscopic biopsy showed a spindle-cell neoplasm composed of bland oval-to-spindle cells arranged in storiform and whorled patterns around branching thin-walled vessels. Immunohistochemically, the tumor cells showed diffuse vimentin expression, focal-to-patchy nuclear β-catenin positivity, scattered Cyclin D1 nuclear positivity, and partial Bcl-2 positivity, whereas STAT6, CD34, cytokeratin, S100, and SMA were negative. These combined morphologic and immunophenotypic findings, although not molecularly confirmed, supported the diagnosis of GPC and argued against recurrent NPC, solitary fibrous tumor, and other spindle-cell neoplasms. Because of extensive skull-base and cavernous-sinus involvement, the lesion was considered unresectable. Empirical palliative docetaxel-cisplatin treatment produced transient symptomatic improvement but was followed by fatal neutropenic sepsis.</p><p><strong>Conclusions: </strong>This case highlights that a vascular submucosal nasopharyngeal mass arising decades after radiotherapy is not necessarily recurrent NPC. In this setting, careful histomorphologic evaluation combined with a practical immunohistochemical panel, particularly focal-to-patchy nuclear β-catenin positivity with STAT6, CD34, and cytokeratin negativity, can support a diagnosis of GPC and help avoid misclassification as recurrent carcinoma or other spindle-cell neoplasms in a previously irradiated field. Because CTNNB1 testing was not performed, the diagnosis should be interpreted as morphologically and immunohistochemically supported rather than molecularly confirmed.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bibliometric and machine learning analyses identify candidate autophagy related therapeutic targets for prostate cancer.","authors":"Chuqi Lin, Peidong Huang, Hui Zhang, Kuncheng Lin, Yuchun Chen, Xinji Li","doi":"10.1007/s12672-026-05616-7","DOIUrl":"https://doi.org/10.1007/s12672-026-05616-7","url":null,"abstract":"<p><strong>Purpose: </strong>Autophagy is increasingly recognized as a promising therapeutic target in prostate cancer (PCa), yet its research landscape has not been systematically evaluated. This study uses bibliometric methods to characterize global research trends and identify emerging hotspots in autophagy-related PCa studies.</p><p><strong>Method: </strong>Publications from 2003 to 2025 were retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, and ScimagoGraphica were used to construct collaborative networks, research frontiers, and development trends. Additionally, clinical trial literature was sourced from PubMed to assess the clinical progress of autophagy-targeted therapy for PCa. The GSE46602 dataset was also employed alongside machine learning techniques to identify autophagy-related genes in PCa.</p><p><strong>Results: </strong>A total of 1,863 publications were identified, contributed by 11,161 authors across 79 countries. The United States and China were leading contributors, with Paul B. Fisher as the most productive author and the National Natural Science Foundation of China as the top funding agency. Current hotspots include epithelial-mesenchymal transition, ferroptosis, drug resistance, non-coding RNA, and berberine. Machine learning analysis identified five core autophagy-related genes: CCL2, CTSB, DAPK1, MYC, and VEGFA. ROC analysis in both training and validation cohorts demonstrated that CTSB, DAPK1, and VEGFA exhibited AUC values greater than 0.75, indicating strong diagnostic potential.</p><p><strong>Conclusions: </strong>Global research on autophagy in PCa is rapidly expanding, especially in ferroptosis crosstalk, RNA regulation, natural compounds, and resistance mechanisms. These findings highlight autophagy as a promising biomarker and therapeutic target in PCa.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global burden and temporal trends of colorectal cancer in East Asia based on the global burden of disease 2023 study.","authors":"Rong Qin, Mingzhu Xie, Rui Gong, Yiyao Duan, Xiang Li, Yulin Tu, Jing Zhou, Jun Hu","doi":"10.1007/s12672-026-05561-5","DOIUrl":"https://doi.org/10.1007/s12672-026-05561-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Colorectal cancer (CRC) remains a significant cause of cancer-related morbidity and mortality in East Asia. The absolute burden is increasing rapidly, driven largely by demographic change, and varies substantially across countries. However, the extent to which long-term trends, population ageing, and socioeconomic development jointly shape the regional CRC burden has not yet been fully quantified. The objective of the present study is to characterise temporal trends and age-specific patterns in CRC burden, in addition to quantifying the contributions of key drivers of change.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study is a population-based observational analysis using estimates from the Global Burden of Disease (GBD) 2023 study, covering China, Japan, Mongolia, the Democratic People's Republic of Korea, and the Republic of Korea from 1990 to 2023. We analyzed incident cases, prevalent cases, deaths, and disability-adjusted life years (DALYs). Age-standardized incidence, prevalence, mortality, and DALY rates were calculated, and their associations with the Socio-demographic Index (SDI) were assessed using Spearman correlation with non-linear curve fitting. Changes in absolute burden were decomposed into contributions from population growth, population ageing, and epidemiological change. Future trends of age-standardized rates to 2050 were projected using autoregressive integrated moving average (ARIMA) models, and temporal changes in mortality trends were evaluated using joinpoint regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From 1990 to 2023, the absolute numbers of incident cases, prevalent cases, deaths, and DALYs from CRC increased across all countries, while trends in age-standardized rates diverged. The age-standardized incidence rate increased markedly in the Republic of Korea (22.98 to 37.78 per 100,000; EAPC 1.71%) and the Democratic People's Republic of Korea (13.88 to 22.60 per 100,000; EAPC 1.48%), with more moderate increases in China and Japan and a slight decline in Mongolia. The age-standardized prevalence rate rose substantially, particularly in the Republic of Korea (96.07 to 224.73 per 100,000; EAPC 3.01%). In contrast, age-standardized mortality and DALY rates declined in most countries but increased in the Democratic People's Republic of Korea. The burden increased steeply with age, especially after 50 years. Significant positive correlations were observed between SDI and all age-standardized rates (ρ = 0.843-0.748, all p &lt; 0.001), with non-linear patterns at higher SDI levels. Decomposition analysis identified population ageing as the primary driver of increasing burden. Projections indicate that the burden will remain high or continue to rise modestly through 2050, with increasing uncertainty. Joinpoint analysis revealed declining mortality trends in China, Japan, and the Republic of Korea, persistent increases in the Democratic People's Republic of Korea, and a recent upturn in ","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic synergies and optimal sequencing of anti‑VEGF plus immune checkpoint inhibition in gastrointestinal cancers.","authors":"Parsa Lorestani, Behrouz Robat-Jazi, Negar Nejati, Kimia Jazi, Ferdos Faghihkhorasani, Anita Khalili, Zahra Karimizadeh, Amirali Kalantari, Ehsan Mirsharifi, Seyed Hesam Hojjat, Armita Jokar-Derisi, Sajjad Ahmadpour","doi":"10.1007/s12672-026-05539-3","DOIUrl":"https://doi.org/10.1007/s12672-026-05539-3","url":null,"abstract":"<p><p>Gastrointestinal (GI) malignancies remain leading causes of cancer-related mortality despite advances in therapeutic strategies. This review was undertaken to provide a comprehensive synthesis of the mechanistic rationale, preclinical evidence, and clinical data supporting the combination of anti-vascular endothelial growth factor (anti-VEGF) agents with immune checkpoint inhibitors (ICIs) in GI cancers, with particular emphasis on optimal sequencing strategies and unresolved challenges. We performed a narrative review of the literature, integrating preclinical studies on tumor microenvironment (TME) dynamics with key phase II/III clinical trials across hepatocellular carcinoma (HCC), colorectal cancer (CRC), gastric/gastroesophageal junction cancers, pancreatic ductal adenocarcinoma, and other GI malignancies. The core rationale for this combination stems from complementary mechanisms: anti-VEGF therapy induces vascular normalization, enhances immune cell infiltration, and reduces immunosuppression within the TME, thereby converting immunologically \"cold\" tumors into \"hot\" tumors that are more responsive to checkpoint blockade. Clinically, the strongest evidence comes from the IMbrave150 trial, which established atezolizumab plus bevacizumab as the new first-line standard of care in advanced HCC, with promising signals also emerging in colorectal and gastric cancers (GC). Nevertheless, significant limitations persist, including overlapping toxicities, adaptive resistance mechanisms, and the lack of validated predictive biomarkers. In this regard, anti-VEGF plus ICI combination therapy offers substantial synergistic potential in GI malignancies. Future progress will depend on biomarker-driven patient selection, refined sequencing and dosing strategies, and rationally designed multi-modal regimens to maximize therapeutic benefit while minimizing harm.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational discovery of curcumin 4'-O-β-D-gentiobioside as a dual anti-virulence and anti-cancer agent.","authors":"Nada H Aljarba, Sayan Chakraborty, Aniruddha Chatterjee, Ashok Kumar Bishoyi, R Roopashree, Daniel Ejim Uti, Esther Ugo Alum","doi":"10.1007/s12672-026-05565-1","DOIUrl":"https://doi.org/10.1007/s12672-026-05565-1","url":null,"abstract":"<p><strong>Objective (s): </strong>Despite the established epidemiological synergy between Porphyromonas gingivalis-induced periodontitis and oral squamous cell carcinoma (OSCC), a critical gap remains in developing single-agent therapeutics that simultaneously neutralize bacterial virulence and suppress host oncogenic signaling. This study aimed to comprehensively evaluate Curcumin 4'-O-β-D-gentiobioside (COG) as a novel, dual-pathway phytochemical intervention targeting the keystone virulence factor RgpB while concurrently disrupting OSCC progression networks.</p><p><strong>Materials and methods: </strong>A multi-modal computational approach was used, including network pharmacology, molecular docking, molecular dynamics simulations, and ADMET profiling. Anti-aging activity was predicted through pharmacological activity modeling.</p><p><strong>Results: </strong>Network pharmacology identified Curcumin 4'-O-β-D-gentiobioside (COG; PubChem CID: 46926100) targeting hub genes (TNF, IL6, EGFR, AKT1), enriching immune regulation, apoptosis, and oxidative stress pathways (FDR < 0.05). Docking revealed strong binding to RgpB (XP GScore: - 9.867 kcal/mol), supported by hydrogen bonds and π-stacking. Molecular dynamics confirmed stability (RMSD: 1.0-1.5 Å; ΔG =  - 14 kcal/mol). COG downregulated pro-inflammatory (CXCL10, MAPK8) and oncogenic (MDM2, BCL2L1) mediators, while enhancing ER stress response (KDELC1, ATF4). ADMET analysis predicted high absorption, negligible neurotoxicity, and no hepatotoxicity/genotoxicity. Predicted anti-aging activities included senolytic, antioxidant, and NF-κB inhibition.</p><p><strong>Conclusion(s): </strong>These results position COG as a promising dual-agent that concurrently neutralizes RgpB virulence, disrupts chronic inflammation, and suppresses OSCC progression, addressing a critical unmet need in oral disease therapeutics. These findings warrant in vivo validation for translation into oral disease therapeutics.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}