Oncology Research最新文献

{"title":"The Role of Immunotherapy in Resectable Non-Small Cell Lung Cancer.","authors":"Francesco Petrella, Andrea Cara, Enrico Mario Cassina, Lidia Libretti, Emanuele Pirondini, Federico Raveglia, Maria Chiara Sibilia, Antonio Tuoro","doi":"10.32604/or.2026.076281","DOIUrl":"https://doi.org/10.32604/or.2026.076281","url":null,"abstract":"<p><p>The advent of immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4 has transformed the therapeutic landscape of advanced non-small cell lung cancer (NSCLC), and recent clinical trials have extended their application to resectable disease. Multiple randomized phase III trials have demonstrated that neoadjuvant and adjuvant immunotherapy, particularly when combined with platinum-based chemotherapy, significantly improves pathological complete response (pCR), major pathological response (MPR), event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) compared to chemotherapy alone. Several key questions remain unresolved-including whether preoperative or postoperative immunotherapy yields superior outcomes, whether adjuvant therapy provides additional benefit after neoadjuvant immune checkpoint inhibitors plus chemotherapy (ICI-CT), and how best to identify the patients most likely to benefit from each strategy. This review will critically examine the current evidence, clinical trial landscape, and future directions for immunotherapy in resectable NSCLC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"2"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818681","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":"Therapeutic Targets for Overcoming BCR::ABL1 Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.","authors":"Masanobu Tsubaki, Taira Matsuo, Rie Komori","doi":"10.32604/or.2025.075217","DOIUrl":"https://doi.org/10.32604/or.2025.075217","url":null,"abstract":"<p><p>Chronic myeloid leukemia (CML) is a hematopoietic malignancy originating from hematopoietic stem cells. It is characterized by the Philadelphia chromosome, which arises from a reciprocal translocation between chromosomes 9 and 22. The breakpoint cluster region::Abelson murine leukemia 1 (BCR::ABL1) fusion protein produced from this chromosome is the main factor responsible for disease onset. Tyrosine kinase inhibitors (TKIs) have led to significant advances in CML treatment and contributed to improved patient survival rates. Nonetheless, a substantial number of patients develop resistance to TKIs, which remains a major challenge in CML therapy. Currently, two mechanisms are considered responsible for TKIs resistance in CML: BCR::ABL1-dependent resistance, involving mutations or overexpression of BCR::ABL1, and BCR::ABL1-independent resistance, which does not depend on BCR::ABL1. This review discusses the recent findings on the resistance mechanisms mediated by BCR::ABL1 mutations. It also focuses on bypass pathways, the B-cell/CLL lymphoma 2 family, tumor suppressor genes, microRNAs, and molecular chaperones as independent resistance mechanisms. Furthermore, the potential for combination therapies targeting these resistance mechanisms is discussed, anticipating further advances in research aimed at overcoming TKI resistance in CML.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"7"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818692","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":"Identify MTDH as a Key Gene of Radio-Resistance in Colorectal Cancer Based on Multi-Omics and Experimental Validation.","authors":"Wei Xu, Yuanyuan Zhang, Yizhi Ge, Yesong Guo","doi":"10.32604/or.2026.075314","DOIUrl":"https://doi.org/10.32604/or.2026.075314","url":null,"abstract":"<p><strong>Objectives: </strong>Radio-resistance hinders the effectiveness of radiotherapy for treating colorectal cancer (CRC) patients. Metadherin (MTDH) is proposed to exert a pivotal role in resistance to radiotherapy in various malignancies. This study aims to investigate the precise impact of MTDH on CRC radio-resistance.</p><p><strong>Methods: </strong>Through a fusion of 14 machine learning algorithms and SHapley Additive exPlanations (SHAP) interpretability analysis, we pinpointed MTDH as a pivotal gene implicated in radio-resistance mechanisms. Subsequently, we investigated MTDH expression in CRC tissues using single-cell RNA sequencing data (scRNA-seq) and bulk transcriptomic data. MTDH level was also examined in tissues from 82 rectal cancer patients who were responsive or non-responsive to radiotherapy. We established radioresistant variants of SW480 and HT29 cells (designated SW480-R and HT29-R), then evaluated their characteristics using cell viability assays, apoptosis measurements, and γ-H2AX foci immunofluorescence. Then, MTDH silencing in radioresistant cells was applied to further investigate the impact of MTDH on regulating radiosensitivity for CRC cells.</p><p><strong>Results: </strong>Machine learning analysis revealed a significant association between MTDH and radio-resistance. Furthermore, multi-omics data confirmed that MTDH expression was significantly upregulated in CRC tissues and, more notably, within the more malignant diploid single-cell subpopulation. Genes associated with MTDH were predominantly enriched in pathways related to damage repair, DNA damage response, epithelial-mesenchymal transition (EMT), and stem cell differentiation, which were known to be critically involved in radio-resistance. Experimental validation confirmed significantly elevated MTDH expression in both radioresistant rectal cancer specimens and corresponding cellular models. High level of MTDH was positively related to several clinicopathological parameters, including tumor stage, differentiation, and lymph node status. Silencing of MTDH inhibited proliferative ability, increased apoptosis, and increased γ-H2AX foci numbers in CRC cells with radiation treatment.</p><p><strong>Conclusion: </strong>This study emphasizes the potential of MTDH as a promising prognostic and therapeutic target in response to radiotherapy for treating CRC patients.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"30"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818338","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":"Multidimensional Regulatory Network of <i>YAP1</i> Driving Malignant Progression in Esophageal Cancer: Molecular Mechanisms and Targeted Therapy: A Review.","authors":"Jun-Hui Chen, Si-Run Du, Chang Liu, Bei-Bei Liu, Hai-Ying Xu, Xin-Ying Ji, Bo Feng, Chun-Zheng Ma, Jun-Hui Guo","doi":"10.32604/or.2026.073484","DOIUrl":"https://doi.org/10.32604/or.2026.073484","url":null,"abstract":"<p><p>Esophageal cancer (EC) ranks among the most lethal gastrointestinal malignancies. Due to challenges in early diagnosis, molecular heterogeneity, and therapeutic resistance, patient prognosis remains extremely poor, necessitating the development of novel biomarkers and therapeutic targets. As a core effector of the Hippo signaling pathway, the potential significance of Yes-associated protein 1 (<i>YAP1</i>) has garnered increasing attention. This paper aims to systematically summarize the multi-omics research, molecular mechanisms, and preclinical/translational evidence for <i>YAP1</i>, covering its activation pathways, biological functions, clinical significance, and therapeutic strategies. We elucidated <i>YAP1</i>'s multidimensional regulatory network in EC, including Hippo-dependent and -independent mechanisms, cross-regulation with environmental risk factors, and its role in malignant phenotypes such as cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and metastasis. The potential of <i>YAP1</i> as a diagnostic, prognostic, and predictive biomarker is evaluated, alongside summarizing its role in mediating chemotherapy, radiotherapy, and immune tolerance mechanisms, along with recent advances in targeted therapies. This provides a theoretical foundation for subsequent basic research and precision medicine translation. As a potential hub in the EC signaling network, it is considered to play a key role in driving tumor progression and treatment resistance through multiple pathways. Targeting <i>YAP1</i> holds broad clinical promise but faces challenges including functional duality, subtype heterogeneity, and complex resistance mechanisms. Future efforts should focus on developing highly selective inhibitors, integrating multi-omics technologies and innovative models to advance clinical translation and provide new strategies for precision treatment of EC patients.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"11"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818599","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":"Mebendazole Attenuates Cellular Invasion in a 3D Culture Model of Meningioma by Disrupting Rho-GTPase-Mediated Microtubule Function.","authors":"Munro Matthew James, López Vásquez Clara Elena, Wickremesekera Agadha, Chan Alex Ho Chuen, Gray Clint Lee","doi":"10.32604/or.2026.074958","DOIUrl":"https://doi.org/10.32604/or.2026.074958","url":null,"abstract":"<p><strong>Objective: </strong>Meningioma is the most common primary brain tumour. Invasion into the brain is a diagnostic feature of grade II meningiomas and is associated with recurrence and poor prognosis. Mebendazole is a microtubule inhibitor typically prescribed as an anthelmintic. However, it has the potential to be repurposed for cancer treatment. Here, we aimed to assess the ability of mebendazole to inhibit meningioma cell invasion.</p><p><strong>Methods: </strong>Primary patient-derived meningioma cell lines were cultured as 3D spheroids and embedded in an extracellular matrix-like matrix as an <i>in vitro</i> model of invasion. Mebendazole-treated and untreated control spheroids were analysed by mass spectrometry-based proteomics.</p><p><strong>Results: </strong>Untreated control spheroids were capable of invasion (9/10 grade I, 10/12 grade II). When treated with mebendazole, invasion was prevented in 89% of samples (8/9 grade I, 9/10 grade II). Mass spectrometry-based proteomics revealed differences between the two grades and between male and female samples within each grade.</p><p><strong>Conclusion: </strong>Overall, mebendazole reduced meningioma cell invasion via Rho GTPase signalling and altered cytoskeletal dynamics in both male and female patient-derived spheroids. Clearly, more research is needed; however, due to its high tolerability, known safety profile, low cost, and ability to attenuate meningioma cell invasiveness, mebendazole has the potential to be a good candidate for being repurposed for the treatment of meningioma.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"21"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818423","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":"Melatonin in Integrative Oncology: Biological Mechanisms, Therapeutic Evidence and Implementation Strategies.","authors":"Jarosław Nuszkiewicz, Joanna Wróblewska, Marek Jóźwiak, Marta Pawłowska","doi":"10.32604/or.2026.077020","DOIUrl":"https://doi.org/10.32604/or.2026.077020","url":null,"abstract":"<p><p>Melatonin, an endogenous indoleamine primarily synthesized in the pineal gland, has emerged as a promising adjunctive agent within integrative oncology due to its pleiotropic biological actions. Beyond its well-known chronobiological functions, melatonin exerts potent redox-regulatory, anti-inflammatory, oncostatic, and immune-modulating effects that are relevant across multiple stages of carcinogenesis and cancer therapy. Oxidative stress (OS), defined as an imbalance between reactive oxygen and nitrogen species (ROS/RNS) generation and antioxidant defenses, plays a central role in DNA damage, protein adduct formation, and lipid peroxidation, ultimately contributing to mutation accumulation, treatment resistance, and tumor progression. Melatonin modulates these OS-related processes through both receptor-dependent and receptor-independent mechanisms, including mitochondrial stabilization, enhancement of antioxidant enzyme activity, inhibition of pro-oxidant pathways, regulation of cell-cycle checkpoints, and promotion of apoptosis in malignant cells while protecting healthy tissues. Preclinical studies demonstrate synergistic interactions between melatonin and chemotherapy, radiotherapy, targeted agents, and immunotherapies, with consistent reductions in treatment toxicity and improvements in tumor control. Emerging clinical evidence supports its potential benefits in quality of life, sleep regulation, fatigue, and selected oncologic outcomes, although heterogeneity in dosing, formulations, and study design remains a key limitation. At the organizational and system levels, successful integration of melatonin into oncology practice requires interdisciplinary collaboration, standardized protocols, clinician awareness, regulatory clarity, and evidence-based implementation strategies. The aim of this narrative review is to synthesize current molecular, experimental, and clinical evidence on melatonin in integrative oncology, with particular emphasis on redox-related mechanisms, therapeutic interactions, and implementation challenges.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"6"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818479","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":"Navigating the Tumor Microenvironment in Colorectal Liver Metastasis: Barriers to Therapy and Emerging Opportunities.","authors":"Pengtao Hu, Junjie Sun, Jian Lu, Chunlei Ge, Hanzhi Sun, Chengyu Lv","doi":"10.32604/or.2026.076013","DOIUrl":"https://doi.org/10.32604/or.2026.076013","url":null,"abstract":"<p><p>Liver metastases from colorectal cancer (CRC) are a primary cause of poor patient prognosis, closely linked to the liver's unique tumor microenvironment (TME). Compared to primary tumors, research on the TME of liver metastases remains insufficient. This review systematically summarizes recent advances in TME research concerning colorectal liver metastases (CRLM), emphasizing its organ-specific characteristics, pivotal role in tumor progression, and influence on treatment response. We delve into the intricate cellular components of the TME-including tumor-associated macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells-and non-cellular constituents such as the extracellular matrix and soluble factors. Furthermore, we explore the multifaceted mechanisms which the TME drives CRLM progression through establishing pre-metastatic niches, facilitating cancer cell colonization, mediating immune evasion, and inducing drug resistance. Additionally, we evaluate therapeutic strategies targeting the TME, including opportunities and challenges in remodeling cellular components, modulating the extracellular matrix, and developing combination therapies. Ultimately, this review aims to provide theoretical foundations and novel insights for developing more effective anti-metastatic therapies, with the goal of improving the prognosis for CRLM patients.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"12"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818526","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":"Comparative Analysis of Tumor Microbiota Identifies a Metastatic-Specific Bacterial Signature, Highlighting <i>Streptococcus</i> spp. As the Predominant Hub across Cancers.","authors":"Nevena Todorovic, Sara Bertorello, Giulia Nannini, Serena Pillozzi, Simonetta Bianchi, Maria Raffaella Ambrosio, Elena Niccolai, Simone Baldi, Amedeo Amedei","doi":"10.32604/or.2026.076380","DOIUrl":"https://doi.org/10.32604/or.2026.076380","url":null,"abstract":"<p><strong>Background: </strong>Cancer remains one of the leading global health challenges, with lung cancer (LC), breast cancer (BC), and colorectal cancer (CRC) among the most prevalent and deadly malignancies. The intratumoral microbiota (IM), a distinct microbial ecosystem within tumor tissues, has recently emerged as a potential modulator of carcinogenesis, immune responses, and metastatic progression. However, comparative cross-cancer analyses remain limited. Therefore, this study aimed to compare the IM across these cancer types, with particular emphasis on distinguishing metastatic from non-metastatic malignancies, to identify tumor-specific microbial signatures with potential relevance for biomarker discovery, patient stratification, and microbiota-informed therapeutic strategies.</p><p><strong>Methods: </strong>We performed 16S rRNA gene sequencing to profile the IM in formalin-fixed, paraffin-embedded (FFPE) samples from 20 BC patients, 20 CRC patients and 15 non-small cell lung cancer (NSCLC) patients.</p><p><strong>Results: </strong>BC samples exhibited the highest genus-level richness, whereas CRC samples showed significantly greater overall alpha diversity, consistent with the microbial complexity of the gut environment. NSCLC samples displayed the most balanced microbial distribution, as reflected by the highest Shannon index value. Stratification by metastatic status revealed distinct microbial signatures: 16 genera were exclusive to metastatic tumors and 49 to non-metastatic ones. In BC specifically, the class Clostridia and the family Burkholderiaceae were enriched in non-metastatic samples, accompanied by functional shifts in pantothenate and coenzyme A biosynthesis, lysine metabolism, and lipid A pathways. Microbial network analysis further revealed differences in ecological community structure and keystone taxa: <i>Streptococcus</i> spp. predominated as hubs in metastatic tumors, whereas <i>Neisseria</i> spp. were central in non-metastatic networks.</p><p><strong>Conclusions: </strong>Overall, our findings highlight cancer-type and metastasis-specific microbial signatures, supporting a potential role for the IM in tumor progression and offering novel avenues for biomarker discovery and therapeutic targeting.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"15"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818081","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":"Cancer-Associated Arterial Thrombosis: Mechanisms and Risk Factors.","authors":"Kassiani Lalechou, Despoina Pantazi","doi":"10.32604/or.2026.074452","DOIUrl":"https://doi.org/10.32604/or.2026.074452","url":null,"abstract":"<p><p>Cancer-associated thrombosis (CAT) is a leading cause of morbidity and mortality among cancer patients. While venous thromboembolic events have been extensively studied due to their higher incidence, arterial thrombosis in cancer patients-referred to as cancer-associated arterial thromboembolism (CA-ATE)-is less well understood but may pose a greater danger. The pathophysiology of CA-ATE involves complex interactions between the tumor microenvironment, cancer cells, patient-related factors, and cancer therapies. Some chemotherapeutic agents, particularly platinum-based compounds (cisplatin, oxaliplatin), gemcitabine, taxanes, and targeted therapies such as tyrosine kinase inhibitors (TKIs), have been associated with an increased risk of arterial thrombosis. In certain patient populations, hormonal therapy and selective estrogen receptor modulators may also contribute to this risk. Additionally, factors such as patient age, cancer type, and stage contribute to an increased risk of arterial thrombosis in this population. Key mechanisms driving CA-ATE include endothelial injury, hypercoagulability, and platelet activation. Certain malignancies, notably lung and pancreatic cancers, are associated with a higher incidence of arterial thrombotic events. The aim of this review is to enhance understanding of the underlying mechanisms of cancer-related arterial thromboembolism and to highlight the various therapeutic, cancer-related, and patient-related factors that contribute to the occurrence of cancer-associated arterial thrombotic events.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"5"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818041","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":"<i>CDCA7</i> Promotes Proliferation and Suppresses Apoptosis in Gastric Cancer via HELLS-Mediated Chromatin Remodeling.","authors":"Jun Jiang, Yi-Ran Li, Xiaoting Wang, Jian Li, Fangzhou Ye, Jiayi Wang, Huanqing Li, Li Feng","doi":"10.32604/or.2026.076051","DOIUrl":"https://doi.org/10.32604/or.2026.076051","url":null,"abstract":"<p><strong>Background: </strong>In various tumor types, cell division cycle-associated 7 (<i>CDCA7</i>) is involved in chromatin remodeling and DNA methylation. However, its biological functions and regulatory mechanisms in gastric cancer (GC) remain unknown. This investigation intended to identify the function of <i>CDCA7</i> in GC progression and elucidate its epigenetic regulatory mechanisms.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) were detected from the GSE19826, TCGA-GC, and GSE56807 datasets. Networks of protein-protein interactions (PPI) and hub genes were discovered by the DMNC and Clustering Coefficient algorithms. Receiver operating characteristic (ROC) analysis and expression profiling were undertaken to determine diagnostic performance. <i>In vitro</i> assays, including CCK-8 assays, clonogenic assays, flow cytometry, dot blots, co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and Western blots, were applied to evaluate the role of <i>CDCA7</i> and its interaction with helicase, lymphoid-specific (<i>HELLS</i>).</p><p><strong>Results: </strong>169 overlapping genes were discovered, enriched in Cell adhesion molecules and ECM-receptor interaction. <i>CDCA7</i> is highly expressed in GC and has high clinical diagnostic value. Knockdown of <i>CDCA7</i> causes apoptosis and suppresses GC cell invasion, migration, and proliferation. Mechanistically, CDCA7 physically interacts with HELLS and promotes HELLS recruitment to chromatin. Knockdown of <i>CDCA7</i> reduces global 5 hmC/5 mC levels and histone methylation (H3K9me3 and H4K20me3), while <i>HELLS</i> overexpression partially reverses these effects. Functionally, <i>HELLS</i> overexpression also partially reverses the antiproliferative and proapoptotic effects of <i>CDCA7</i> knockdown.</p><p><strong>Conclusion: </strong><i>CDCA7</i> promotes GC progression by interacting with <i>HELLS</i> to regulate DNA methylation and chromatin stability, suggesting that the <i>CDCA7</i>-<i>HELLS</i> axis may serve as a potential diagnostic biomarker and therapeutic target for GC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"32"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818593","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}