Oncology Research最新文献

{"title":"Bladder Cancer Biomarkers: Recent Advances in Early Detection, Treatment Prediction, and Prognosis.","authors":"Ziyou Bai, Xiaoyan Song, Jiayin Sun, Wen Xiao, Xiangui Meng, Wei Dong","doi":"10.32604/or.2026.086230","DOIUrl":"10.32604/or.2026.086230","url":null,"abstract":"<p><p>Bladder cancer (BC) is a prevalent malignancy characterized by a high recurrence rate and the necessity for long-term surveillance demands, creating a need for accurate yet practical tools for early detection and monitoring. While current standards including cystoscopy, urinary cytology, and imaging remain indispensable, their clinical utility is constrained by invasiveness, suboptimal sensitivity for selected lesions or low-grade lesions, inter-observer variability, and cumulative costs. Currently, biomarker research has expanded from single protein assays to multi-analyte strategies encompassing DNA, RNA, proteins, extracellular vesicle-associated cargo, and metabolomics signatures. This review synthesizes recent advances in diagnostic, surveillance, prognostic, and treatment-predictive biomarkers, with emphasis on assay principles, analytical platforms and reported performance where available. Furthermore, we delineate critical barriers to translation, including limited prospective multicenter validation, heterogeneous pre-analytical workflows, inconsistent thresholds, and the persistent trade-off between sensitivity and specificity in real-world benign urologic conditions. Ultimately, while emerging biomarkers and multi-omics panels hold transformative potential as non-invasive adjuncts in risk-adapted clinical pathways, their routine adoption is contingent upon rigorous clinical integration and standardized validation.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"19"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sevoflurane Inhibits Colon Cancer Progression by Inducing Cell Autophagy and Apoptosis through the ROS/Nrf2/P62 Pathway.","authors":"Xiangui Liu, Jianhua Liu, Qingbin Meng, Yongsheng Shao","doi":"10.32604/or.2026.082954","DOIUrl":"10.32604/or.2026.082954","url":null,"abstract":"<p><p><b>Objectives:</b> There is debate over the effect of sevoflurane (SEV) on different cancers. This study aims to explore SEV's role in colon cancer (CC) progression. <b>Methods:</b> The CC cell lines were treated with SEV at concentrations of 1.7%, 3.4%, and 5.1%. Cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation assay, flow cytometry, Western blot, scratch assay, and Transwell assay. A xenograft tumor model was established to evaluate the effect of SEV <i>in vivo</i>. Expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), p62 (sequestosome-1), microtubule-associated protein 1 light chain 3 isoform II to I ratio (LC3-II/I), Beclin-1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) were measured. N-acetyl-L-cysteine (NAC), a ROS scavenger, was applied to determine whether ROS-dependent Nrf2/p62 signaling participated in this process. <b>Results:</b> SEV inhibited CC cell proliferation, colony formation, migration, and invasion. At 5.1% SEV, cell proliferation was reduced by 54.0% (<i>p</i> < 0.001); colony formation decreased by 55.0% (<i>p</i> < 0.001); and wound closure rates dropped from 78.3% to 24.6% (<i>p</i> < 0.001) in HCT116 cells. Similar trends were observed in SW480 cells. Invaded cells were also significantly reduced in both cell lines (<i>p</i> < 0.001). SEV also induced CC apoptosis. In the xenograft model, treatment with SEV significantly suppressed tumor progression, as evidenced by reductions in both tumor volume and weight (<i>p</i> < 0.001). Mechanistically, SEV increased the LC3-II/I ratio and Beclin-1 expression, while decreasing Nrf2 and p62 expression both <i>in vitro</i> and <i>in vivo</i>. Moreover, NAC reversed the SEV-induced effects <i>in vitro</i>. <b>Conclusion:</b> SEV inhibits CC progression by inducing autophagy and apoptosis via the ROS/Nrf2/p62 pathway.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"18"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Honokiol Suppresses Stemness and Sensitizes Triple-Negative Breast Cancer to Chemotherapy via YAP/TAZ-TEAD Inhibition.","authors":"Jiang-Nan Xia, Shan-Dong Zhu, Wei-Ling Qu, Yi-Lin Hu, Wen-Yi Ma, Wenyan Wang, Qian-Lan Huang, Bing-Yuan Lin, Jia-En Guo, Ying-Wei Li","doi":"10.32604/or.2026.084576","DOIUrl":"10.32604/or.2026.084576","url":null,"abstract":"<p><p><b>Objectives:</b> As an aggressive subtype of breast cancer, triple-negative breast cancer (TNBC) is constrained by the limited availability of effective treatments and the absence of well-validated therapeutic targets. This study aimed to explore whether honokiol, a potent YAP/TAZ inhibitor, suppresses stem cell-like properties and enhances chemotherapeutic efficacy in TNBC by blocking YAP/TAZ-TEAD transcriptional complex. <b>Methods:</b> Through both <i>in vitro</i> and <i>in vivo</i> models of TNBC, the current study examined how honokiol influences cell proliferation, cancer stem cell (CSC) traits, and paclitaxel sensitivity. To uncover the molecular mechanisms, we analyzed the transcript levels and protein abundance of core YAP/TAZ-TEAD pathway members, including YAP, TAZ, TEADs, ANKRD1, and CYR61. Furthermore, we conducted immunofluorescence staining to examine the nuclear localization of YAP/TAZ. Potential direct interactions were identified using molecular docking, which also predicted the binding affinity between honokiol and the TAZ-TEAD complex. <b>Results:</b> Honokiol markedly suppressed the viability and stemness of TNBC cells. It also improved the antitumor efficacy of paclitaxel in both TNBC cells and xenograft models. Mechanistically, honokiol may directly target the TAZ-TEAD complex, as indicated by molecular docking analysis. This interaction led to decreased YAP/TAZ protein levels and blockade of their nuclear accumulation, thereby suppressing the downstream transcriptional targets ANKRD1 and CYR61 in TNBC cells. <b>Conclusion:</b> Collectively, our findings suggest that honokiol is a promising therapeutic agent against TNBC, acting at least in part by suppressing the transcriptional activity of the YAP/TAZ-TEAD complex, thus attenuating cancer stemness and overcoming chemoresistance. These findings highlight honokiol's translational potential.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"23"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cGAS Downregulation Contributes to EGFR-TKI Resistance in NSCLC through the p-Nrf2-SIRT3-ROS/Ferroptosis Axis.","authors":"Yawan Zi, Huilin Yu, Xiaohui Wang, Yuezhou Zhang, Shengxin Fan, Jiukang Li, Jian Wang, Ke Liao, Hong Chen","doi":"10.32604/or.2026.082400","DOIUrl":"10.32604/or.2026.082400","url":null,"abstract":"<p><p><b>Background:</b> Although epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibition produces substantial initial benefit in EGFR-mutant non-small cell lung cancer, durable disease control is frequently compromised by the emergence of drug-resistant tumor cells. We therefore examined whether loss of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) supports the resistant phenotype by altering redox control and the cellular threshold for ferroptotic injury. <b>Methods:</b> The Gene Expression Omnibus (GEO) datasets GSE172002 and GSE236654 were analyzed to identify resistance-associated pathways. cGAS was depleted in parental cells and restored in resistant derivatives, followed by phenotypic, redox, mitochondrial, and signaling assessments in cultured cells and xenografts; pathway relationships were further examined by rescue experiments and structural modeling. <b>Results:</b> Bioinformatics analysis indicated significant alteration of DNA repair-related pathways in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-resistant models. Resistant PC-9/GR and H1975/OR cells displayed increased half-maximal inhibitory concentration (IC₅₀) values and attenuated inhibition of phosphorylated EGFR (p-EGFR), Phosphorylated Protein Kinase B1 (p-AKT1), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) after matched EGFR-TKI treatment. In parental cells, EGFR-TKI exposure was associated with increased DNA damage, cytosolic double-stranded DNA (dsDNA) accumulation, cGAS induction, ferroptosis-related staining patterns, reduced glutathione (GSH), and increased malondialdehyde (MDA), whereas these changes were less evident in resistant cells and were partly attenuated by Ferrostatin-1. Functionally, cGAS knockdown was associated with enhanced proliferative, migratory/invasive, and xenograft growth phenotypes, together with a redox pattern consistent with reduced ferroptosis susceptibility. Conversely, cGAS overexpression in resistant cells produced opposite effects. Altering cGAS abundance redistributed total and Ser40-phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2) between cellular compartments and concurrently changed sirtuin 3 (SIRT3) abundance and deacetylase activity. Nrf2 or SIRT3 manipulation partially reversed cGAS-associated phenotypes. <b>Conclusions:</b> These findings identify low cGAS abundance as a feature of the resistant state and support its involvement in an Nrf2-SIRT3-dependent antioxidant program that raises the threshold for ferroptotic damage.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"17"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastatic Triple Negative Breast Cancer: Navigating a Rapidly Evolving Therapeutic Landscape.","authors":"Iseult M Browne, Monica Esteban Garcia, Alicia F C Okines","doi":"10.32604/or.2026.082829","DOIUrl":"10.32604/or.2026.082829","url":null,"abstract":"<p><p>Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor, and HER2 expression, and carries a disproportionate burden of breast cancer-related mortality due to its aggressive biology and historically limited therapeutic options. The treatment landscape of metastatic TNBC has undergone a fundamental transformation over the past decade, driven by immune checkpoint inhibitors, antibody-drug conjugates (ADCs), and the identification of actionable genomic alterations. This review provides a comprehensive, clinically oriented appraisal of the current and emerging therapeutic landscape of metastatic TNBC, encompassing its molecular underpinnings and tumour microenvironment biology. We critically evaluate the evolving roles of immune checkpoint inhibition, ADCs, PARP inhibitors, and novel targeted approaches, discuss mechanisms of resistance and biomarker limitations, and propose a framework for rational, biomarker-guided treatment selection and sequencing to support evidence-based clinical decision-making in this rapidly evolving field.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"3"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanorobots and Exosomes: Driving the New Frontier for Bladder Tumors through Non-Coding RNAs.","authors":"Lorenzo Spirito, Cristina Quintavalle, Paola Coppola, Matteo Esposito, Francesco Esposito, Gabriella De Vita, Pierlorenzo Pallante","doi":"10.32604/or.2026.078045","DOIUrl":"10.32604/or.2026.078045","url":null,"abstract":"<p><p>Because of its limited treatment choices and high recurrence rates, bladder cancer (BCa) presents a significant clinical issue. As a result, current research is concentrated on creating novel approaches for early diagnosis and more specialized treatments. Nanorobots hold significant potential as precise medicine-delivery systems and as <i>in situ</i> diagnostic vectors within this dynamic environment. Personalized treatments are becoming increasingly feasible thanks to new insights into the molecular pathways driving tumor growth, revealed through studies on exosomes and non-coding RNAs (ncRNAs), however, their true potential lies in integrating these findings. This review analyzes the role of nanorobots, exosomes and ncRNAs in BCa and, more importantly, proposes a synergistic framework where active nanorobots are used for the targeted delivery of therapeutic exosomes (loaded with ncRNAs), overcoming the physiological limitations of intravesical administration. The interplay between nanorobots, exosomes and ncRNAs outlines a coherent and synergistic therapeutic approach with nanorobots enabling active navigation, exosomes offering stable and biocompatible loading, and ncRNAs providing the precision molecular functions required for targeted intervention. Their integration constitutes the core rationale driving this emerging approach and this technological convergence may open new avenues for precision diagnosis and targeted therapy. Incorporating these state-of-the-art technologies could ultimately transform the treatment of BCa and greatly enhance patient outcomes and quality of life. The aim of this review is to evaluate the current evidence on these three technologies and to define an integrated strategy that addresses existing clinical barriers and advances precision medicine in BCa.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"8"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promoter Hypermethylation-Driven NPHS2 Silencing Promotes Immune Escape and Sunitinib Resistance in Clear Cell Renal Cell Carcinoma.","authors":"Shangjian Li, Qipeng Han, Xinying Sun, Rongrong Yu","doi":"10.32604/or.2026.080228","DOIUrl":"10.32604/or.2026.080228","url":null,"abstract":"<p><p><b>Objective:</b> Renal cell carcinoma is a common malignancy of the urinary system. In this study, we analyzed a public clear cell renal cell carcinoma (ccRCC) dataset and identified Nephrosis 2, idiopathic, steroid-resistant (NPHS2) as a candidate gene to investigate whether epigenetic dysregulation of NPHS2 is associated with tumor microenvironment remodeling. <b>Methods:</b> Differential expression analysis was first performed on GSE68417 using GEO2R. In addition, clinical samples and cell-based assays were used to evaluate changes in NPHS2 expression and promoter methylation following 5'-Aza-CdR treatment. Subsequently, 786-O and A498 cells were obtained, and sunitinib-resistant 786-O/R and A498/R sublines were established. Lentiviral vectors with abnormal expression of NPHS2 were transfected into 786-O, A498, 786-O/R, and 498-R cells to detect changes in biological behaviors such as cell activity and epithelial-mesenchymal transition (EMT). Finally, a ccRCC tumor-bearing mouse model was constructed and intervened with lentiviral vectors with abnormal expression of NPHS2. <b>Results:</b> A total of 159 differentially expressed genes (DEGs) were identified in the GSE68417 dataset, and NPHS2 was included in all morphological changes related to cell epigenetic modifications. 5'-Aza-CdR markedly increased NPHS2 protein expression in 786-O cells (<i>p</i> < 0.05). Meanwhile, there was a high methylation phenomenon in the promoter region of the NPHS2 gene in ccRCC tissue (<i>p</i> < 0.05). <i>In vitro</i>, NPHS2 overexpression suppressed malignant cell behavior, attenuated EMT, and weakened immune evasion in ccRCC cells (<i>p</i> < 0.05). Finally, upregulating NPHS2 could inhibit the growth of ccRCC (<i>p</i> < 0.05) without causing significant changes in liver and kidney functions or malignant pathological damage in mice. <b>Conclusion:</b> These findings support an association between promoter hypermethylation and NPHS2 downregulation in ccRCC and suggest that NPHS2 loss may contribute to immune-evasive features and reduced sunitinib sensitivity. Further multicohort and mechanistic studies are warranted.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"25"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Long Noncoding RNA UCA1 Targets miR-122 to Promote Proliferation, Migration, and Invasion of Glioma Cells.","authors":"","doi":"10.32604/or.2026.092120","DOIUrl":"https://doi.org/10.32604/or.2026.092120","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504017X14934860122864.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"30"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicities of Fruquintinib in Gastrointestinal Malignancies: A Systematic Review and Meta-Analysis.","authors":"Daniel Thomas Jones, Tajveer Sangha, Arman Manjikian, Micheal Ghobrial, Qasim Shawesh, Emaan Tiwana, Emi Hearn, Arash Latif, Elaine Tupas, Aishwarya Hanspal, Rishi Kumar Nanda, Ramaditya Srinivasmurthy, Jason Ta, Meghana Pandit, Charles Abraham Joseph Larson, Kyaw Zin Thein","doi":"10.32604/or.2026.078524","DOIUrl":"10.32604/or.2026.078524","url":null,"abstract":"<p><p><b>Backgrounds:</b> Fruquintinib is a selective vascular endothelial growth factor receptor (VEGFR)-1/2/3 inhibitor approved for previously treated metastatic colorectal cancer. As its use expands across gastrointestinal (GI) malignancies and combination regimens, randomized evidence is needed to define the toxicity profile most relevant to clinical monitoring, particularly hypertension, dermatologic toxicity, renal toxicity, bleeding, and thrombotic events. The objective of this study was to synthesize randomized controlled trial evidence to quantify the incidence and relative risk of key toxicities associated with fruquintinib in gastrointestinal malignancies. <b>Methods:</b> MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception through 1 January 2026 for phase II-III randomized controlled trials of fruquintinib in GI cancers reporting hypertension, proteinuria, hemorrhage, venous thromboembolism (VTE), and hand-foot skin reaction or palmar-plantar erythrodysesthesia (HFSR/PPE). Trial-reported CTCAE adverse events were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using Mantel-Haenszel random-effects models. Exploratory subgroup analyses were performed in metastatic colorectal cancer (mCRC). <b>Results:</b> Four randomized trials (n = 1872) were included. Fruquintinib significantly increased grade ≥3 hypertension (RR 9.01, 95% CI 4.67-17.40) and grade ≥3 HFSR/PPE (RR 26.00, 95% CI 6.42-105.29). Any-grade proteinuria was also increased (RR 1.89, 95% CI 1.30-2.74). Grade ≥3 hemorrhage occurred at low absolute rates and was numerically higher with fruquintinib, but the pooled estimate did not reach statistical significance (RR 1.82, 95% CI 0.92-3.61). VTE estimates were imprecise because of sparse events (any-grade VTE: RR 1.23, 95% CI 0.53-2.88; grade ≥3 VTE: RR 1.96, 95% CI 0.52-7.36). <b>Conclusions:</b> In randomized evidence across GI malignancies, the principal safety signals associated with fruquintinib are grade ≥3 hypertension and grade ≥3 HFSR/PPE, together with increased any-grade proteinuria. Grade ≥3 hemorrhage was uncommon and numerically higher, whereas VTE estimates remained imprecise. These findings support early blood pressure optimization, proactive dermatologic management, routine urinalysis monitoring, and individualized assessment of bleeding and thrombotic risk when initiating therapy.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"9"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Reprogramming in Gastric Cancer Immunity Mechanisms and Therapeutic Implications.","authors":"Xiangyang Wang, Ying Wu, Yutong Fu, Ejakpovi Emmanuel Oghenefejiro, Zakari Shaibu, Cunxi Li, Qi Zhou, Liang Yin","doi":"10.32604/or.2026.087144","DOIUrl":"10.32604/or.2026.087144","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a leading cause of global cancer mortality, with progression and therapy resistance heavily influenced by the dynamic tumor microenvironment (TME). Despite advances in surgical techniques, chemotherapy, targeted therapy, and immunotherapy, overall survival for advanced disease remains poor, underscoring the need for a deeper understanding of resistance mechanisms. A hallmark of the TME is metabolic reprogramming, which sustains tumor growth and actively shapes an immunosuppressive landscape. This review aims to detail the coordinated metabolic adaptations of GC cells, cancer-associated fibroblasts (CAFs), and immune cells within the TME, focusing on nutrient competition, immunosuppressive metabolite accumulation, and dysregulated lipid metabolism. We analyze how glucose depletion, lactate accumulation, and amino acid deprivation establish a hostile metabolic niche that impairs cytotoxic T lymphocyte (CTL) function while paradoxically supporting regulatory T cells (Tregs), M2-like tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs). We examine four major immunosuppressive metabolic pathways, lactate, adenosine, tryptophan-kynurenine, and arginine and demonstrate their convergence on immune checkpoint upregulation, forming an integrated metabolic-immune checkpoint axis. These pathways establish a self-reinforcing immunosuppressive circuit that drives T cell exhaustion and limits immune checkpoint blockade efficacy. We highlight emerging therapeutic strategies targeting this crosstalk, including inhibitors of glycolysis, glutaminolysis, indoleamine 2,3-dioxygenase 1 (IDO1), and adenosine signaling, often combined with immunotherapy. The metabolic supply-demand mismatch explains why certain interventions can revive effector cells while potentially harming other cell types. Finally, we discuss challenges and future directions, emphasizing the need for spatially resolved metabolic profiling, biomarker-driven patient stratification, and personalized therapies to overcome metabolic immunosuppression and improve clinical outcomes in GC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 10","pages":"10"},"PeriodicalIF":4.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}