Oncology Research最新文献

{"title":"The Double-Edged Sword of Genomic DNA Methylation: Orchestrating Gastric Carcinogenesis and Shaping Precision Oncology.","authors":"Xuan Chen, Chao Luo, Wei Wen","doi":"10.32604/or.2026.079753","DOIUrl":"10.32604/or.2026.079753","url":null,"abstract":"<p><p>This article systematically elaborates on the dual role of DNA methylation in the initiation and progression of gastric cancer and its potential clinical applications in precision oncology. As a core epigenetic mechanism, DNA methylation drives the multistage development of gastric cancer through the coordinated dysregulation of genome-wide hypomethylation and promoter-specific hypermethylation, playing a key role in chronic inflammation and epigenetic reprogramming, particularly in the context of <i>Helicobacter pylori</i> infection. The article focuses on analyzing the central pathogenic mechanisms of DNA methylation, including the silencing of tumor suppressor genes, induction of genomic instability, promotion of the CpG island methylator phenotype, and facilitation of epithelial-mesenchymal transition. It further explores the clinical utility of DNA methylation as a biomarker for early diagnosis, prognosis evaluation, recurrence monitoring, and prediction of therapeutic response in gastric cancer. Moreover, the article reviews epigenetic therapeutic strategies represented by hypomethylating agents and their potential and challenges when combined with chemotherapy or immunotherapy, envisioning an integrated precision medicine model based on methylation profiling.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"3"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796376","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":"Impact of <i>IL31RA</i> Genetic Variants and Expression on Metastatic Progression in Oral Cavity Squamous Cell Carcinoma.","authors":"Hsueh-Ju Lu, Chiao-Wen Lin, Chun-Yi Chuang, Chun-Wen Su, Shun-Fa Yang","doi":"10.32604/or.2026.080527","DOIUrl":"10.32604/or.2026.080527","url":null,"abstract":"<p><p><b>Background:</b> Interleukin-31 receptor alpha (IL31RA) has been implicated in cancer progression and tumor cell migration, but its genetic associations across cancers remain unclear. This study aimed to examine <i>IL31RA</i> polymorphisms in relation to lymph node involvement in oral cavity squamous cell carcinoma (OCSCC). <b>Methods:</b> In this case-control study, 2845 participants were enrolled, including 1352 patients with OCSCC and 1493 cancer-free controls. Associations between <i>IL31RA</i> SNPs and OCSCC susceptibility and clinicopathological characteristics were evaluated. Functional analyses, including cell migration assays, together with bioinformatic database analyses, were performed to investigate the biological significance of IL31RA and genotype-expression correlations. Logistic regression and other appropriate statistical methods were used to assess these associations. <b>Results:</b> <i>IL31RA</i> polymorphisms did not significantly influence OCSCC development. However, subsite-specific analysis revealed that gingival cancer patients with minor alleles at rs6876491 and rs10055201 had significantly higher lymph node involvement rates than wild-type carriers. <i>IL31RA</i> rs6876491 was also an independent predictor of lymph node involvement in gingival cancer after adjusting for clinical characteristics, with adjusted odds ratios of 2.172 (95% Confidence Interval: 1.095-4.310). Bioinformatic databases also showed that minor genotypes correlated with increased IL31RA expression. Patients with higher IL31RA expression tended to have poorer survival in head and neck squamous cell carcinoma (HNSCC) based on TCGA public database analyses (<i>p</i> = 0.053). Moreover, functional studies confirmed that IL31RA overexpression enhanced cellular migration (<i>p</i> < 0.05), while knockdown suppressed migratory capacity (<i>p</i> < 0.05). <b>Conclusions:</b> <i>IL31RA</i> polymorphisms may be associated with an increased propensity for lymph node involvement, particularly in gingival cancer, suggesting that IL31RA may have potential clinical relevance in OCSCC progression.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"17"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795990","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: The Long Noncoding RNA HOTAIR Promotes Colorectal Cancer Progression by Sponging miR-197.","authors":"","doi":"10.32604/or.2026.090481","DOIUrl":"https://doi.org/10.32604/or.2026.090481","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504017X15105708598531.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"31"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796264","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: Knockdown of Long Noncoding RNA TUG1 Inhibits the Proliferation and Cellular Invasion of Osteosarcoma Cells by Sponging miR-153.","authors":"","doi":"10.32604/or.2026.090479","DOIUrl":"https://doi.org/10.32604/or.2026.090479","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504017X14908298412505.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"30"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796247","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":"Targeting Cytoskeleton and Cell Motility: Past and Novel Strategies for Cancer Therapy.","authors":"Lucrezia Paradisi, Lorenza Trabalzini, Federica Finetti","doi":"10.32604/or.2026.082155","DOIUrl":"10.32604/or.2026.082155","url":null,"abstract":"<p><p>Cytoskeletal reorganization is fundamental to essential cellular processes, including shape maintenance, migration, adhesion cytokinesis, and phagocytosis, and its dysregulation is a hallmark of tumor progression. In cancer cells, altered cytoskeletal dynamics promote invasion and genomic instability resulting from mitotic defects. The actin and microtubule cytoskeletons are highly dynamic polymer networks that organize intracellular architecture, establish polarity, and generate the mechanical forces required for cell division and motility. Their dysregulation disrupts normal cell behavior and facilitates tumor invasion and metastasis. The cytoskeleton therefore represents a key source of potential therapeutic targets for inhibiting metastatic dissemination. This review focuses on recent anticancer strategies targeting cytoskeletal and motility-associated pathways, including microtubule-directed agents, actin-modulating compounds, inhibitors of focal adhesion signaling, modulators of intermediate filament dynamics, and regulators of cytoskeletal crosstalk. Collectively, these strategies underscore the central role of cytoskeleton in cancer progression and highlight its potential as a promising therapeutic target.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"2"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796321","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":"Differential Tumor Response and Conversion Outcomes Associated with First-Line Biologic Strategies in Liver-Limited <i>RAS</i> Wild-Type Metastatic Colorectal Cancer.","authors":"Shih-Wei Chiang, Ming-Cheng Chen, Chang-Lin Lin, Yi-Lin Huang, Feng-Fan Chiang, Shun-Fa Yang","doi":"10.32604/or.2026.085229","DOIUrl":"10.32604/or.2026.085229","url":null,"abstract":"<p><p><b>Background:</b> Anti-EGFR therapy is widely used as first-line treatment for <i>RAS</i> wild-type metastatic colorectal cancer (mCRC), particularly in patients with left-sided tumors. In liver-limited disease, maximizing tumor shrinkage may facilitate conversion to resectability; however, comparative real-world evidence among panitumumab, cetuximab, and bevacizumab remains limited. This study aimed to compare the clinical outcomes of these biologic agents in patients with <i>RAS</i> wild-type mCRC. <b>Methods:</b> We retrospectively analyzed 241 patients with <i>RAS</i> wild-type mCRC treated with first-line chemotherapy plus panitumumab (<i>n</i> = 76), cetuximab (<i>n</i> = 80), or bevacizumab (<i>n</i> = 85) between 2016 and 2024. Outcomes included depth of response (DpR), objective response rate (ORR), disease control rate (DCR), conversion surgery rate, progression-free survival (PFS), and overall survival (OS). <b>Results:</b> Overall, panitumumab demonstrated superior tumor response, achieving the highest ORR (69.7%) and conversion surgery rate (34.2%), although PFS and OS were comparable among treatment groups. In patients with liver-limited disease, panitumumab was associated with a higher conversion surgery rate than bevacizumab (50.0% vs. 19.4%) and a trend toward longer OS. Right-sided primary tumors and <i>BRAF</i> mutation remained independent predictors of poorer OS. <b>Conclusions:</b> Panitumumab-based therapy was associated with deeper tumor shrinkage and higher conversion rates, particularly in liver-limited mCRC. These findings suggest that greater cytoreduction may increase opportunities for local treatment in selected patients. However, given the retrospective nature of the study, the findings should be considered hypothesis-generating and require prospective validation.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"23"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795964","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":"Invariant Natural Killer T Cell Therapy Attenuates Systemic Inflammation and Improves Transarterial Chemoembolization Outcomes in Hepatocellular Carcinoma.","authors":"Xiaoxia Wang, Shuo Wang, Chendi Liang, Huili Wu, Songtao Liu, Jinhuan Wang, Jun Lu","doi":"10.32604/or.2026.082815","DOIUrl":"10.32604/or.2026.082815","url":null,"abstract":"<p><p><b>Background:</b> Invariant natural killer T (iNKT) cells show promise as immunotherapeutic agents for solid tumors, and our prior study demonstrated that combining iNKT-cell therapy with transarterial chemoembolization (TACE) achieved a 58.3% objective response rate (ORR) in hepatocellular carcinoma (HCC). This study further examines iNKT-mediated immune modulation of post-TACE survival dynamics and associated prognostic biomarkers. <b>Methods:</b> Clinical data and peripheral blood samples were obtained from 77 HCC patients in Beijing you'an Hospital between 2018-2023, including 38 receiving TACE alone and 39 receiving combined iNKT-cell/TACE therapy. Serial measurements included: Hematological parameters; Liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin]; Inflammatory markers [C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR)]; Cytokine profiling [Interferon-gamma (IFN-γ), Interleukin-6 (IL-6), Interleukin-10 (IL-10)]. Potential Prognostic factors for progression-free survival (PFS) were identified through univariate/multivariate Cox regression. A risk-score model was derived using significant covariates from the multivariate analysis. Model performance was evaluated by time-dependent receiver operating characteristic (ROC) analysis [Area Under the Curve (AUC) calculation] and Kaplan-Meier survival stratification with log-rank testing. <b>Results:</b> The TACE group exhibited decreased lymphocytes but increased neutrophils/monocytes post-treatment, whereas iNKT + TACE maintained stable counts. Systemic inflammation indices [NLR/systemic immune-inflammation Index (SII)/systemic inflammation response index (SIRI)] rose significantly in TACE alone (all <i>p</i> < 0.05) but remained stable in iNKT + TACE. Cytokine profiling revealed reduced IL-6/IL-10 (<i>p</i> < 0.001/<i>p</i> = 0.012) and elevated IFN-γ/tumor necrosis factor-alpha (TNF-α) (<i>p</i> < 0.01/<i>p</i> < 0.001) in iNKT + TACE vs. TACE. Multivariate analysis identified lymphocyte count (HR = 0.18, 95%CI 0.04-0.76, <i>p</i> = 0.02), IL-6 (HR = 2.57, 95%CI 1.03-6.86, <i>p</i> = 0.04), and IFN-γ (HR = 0.14, 95%CI 0.02-0.98, <i>p</i> = 0.04) as independent PFS predictors. The risk model demonstrated strong discrimination (AUC = 0.891, 95%CI 0.73-1.00), with median PFS of 9.5 vs. 3.0 months for low- vs. high-risk groups (log-rank <i>p</i> < 0.01) in iNKT + TACE group. <b>Conclusions:</b> iNKT cell therapy stabilizes peripheral lymphocyte counts and attenuates TACE-induced inflammation in HCC. The combined evaluation of lymphocyte levels, IL-6, and IFN-γ represents a promising prognostic biomarker panel for PFS in iNKT + TACE-treated patients.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"26"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795983","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":"Prognostic Significance and Functional Role of PPIB in a Retrospective Cohort of Patients with Advanced Gastric Cancer.","authors":"Kyungeun Kim, Eunho Cho, Eun Joo Chung, Kwon-Ho Song, Tae Woo Kim, Seoung Wan Chae, Joon-Yong Chung","doi":"10.32604/or.2026.083437","DOIUrl":"10.32604/or.2026.083437","url":null,"abstract":"<p><p><b>Objectives:</b> Gastric cancer remains a major global health burden, and robust biomarkers are needed to improve risk stratification. Although peptidyl-prolyl isomerase B (PPIB) has been suggested as a potential oncogenic factor, its clinical utility in gastric cancer remains unclear. This study aims to evaluate the clinicopathological and prognostic significance of <i>PPIB</i> mRNA expression and delineate its functional role in driving tumor progression. <b>Methods:</b> <i>PPIB</i> mRNA expression was evaluated in a retrospective cohort of 497 gastric cancer patients using RNAscope <i>in situ</i> hybridization and digital image analysis. Functional roles and underlying mechanism were assessed through siRNA-mediated knockdown, plasmid-driven overexpression, and STAT3-targeted rescue experiments <i>in vitro</i>. <b>Results:</b> High <i>PPIB</i> expression was significantly associated with aggressive clinicopathological features, including larger tumor size, advanced T stage, and lymph node metastasis. Patients with high <i>PPIB</i> expression had significantly worse progression-free survival (PFS) and overall survival (OS) compared to those with low expression, particularly in advanced stage. Multivariate analysis identified high <i>PPIB</i> expression as an independent predictor of poor PFS and OS. Functionally, <i>PPIB</i> silencing suppressed gastric cancer cell proliferation, migration, and invasion, whereas its overexpression enhanced these oncogenic behaviors in both cancerous and non-tumorigenic cells. These aggressive phenotypes were effectively mitigated through STAT3 targeted functional rescue experiments. <b>Conclusions:</b> PPIB is a robust independent prognostic biomarker for gastric cancer, especially in advanced stages. Its role in driving aggressive phenotypes via STAT3 signaling underscore its potential for risk stratification and as a therapeutic target.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"22"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796193","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":"PSMB9 Promotes the Malignant Progression of Colorectal Cancer by Regulating the PI3K/Akt Pathway.","authors":"Wen Gao, Xingyu Zheng, Yanan Hu, Rui Zou, Yongan Zhou, Xiang Song","doi":"10.32604/or.2026.082652","DOIUrl":"10.32604/or.2026.082652","url":null,"abstract":"<p><p><b>Background:</b> As a core component of the immunoproteasome, the β1i subunit (proteasome 20S subunit beta 9, PSMB9) is involved in antigen processing and presentation and regulates anti-tumor immune responses. PSMB9 is aberrantly overexpressed in colorectal cancer. However, the precise mechanisms through which PSMB9 contributes to the initiation, progression, and immune regulation of colorectal cancer remain unclear. This study aims to investigate the expression characteristics and biological functions of PSMB9 in colorectal cancer, and to further elucidate the molecular pathways underlying its role in colorectal cancer initiation and progression. The findings are expected to provide a theoretical basis for the development of targeted therapeutic strategies against colorectal cancer. <b>Methods:</b> PSMB9 expression in colorectal cancer was analyzed using the TCGA, GEO, GEPIA, and HPA databases, and further validated in normal colonic epithelial cells and colorectal cancer cell lines by RT-qPCR and Western blot. Lentiviral transduction was used to establish stably transduced HCT116 and SW480 cell lines with PSMB9 knockdown and overexpression, respectively. Cell proliferation, migration, and invasion were assessed by CCK-8, colony formation, wound healing, and Transwell assays. Key proteins of the PI3K/Akt signaling pathway were detected by Western blot. <b>Results:</b> PSMB9 was significantly upregulated at both the mRNA and protein levels in colorectal cancer tissues and cell lines. PSMB9 knockdown significantly inhibited the proliferation, migration, and invasion of colorectal cancer cells, while overexpression enhanced these malignant phenotypes. Mechanistically, PSMB9 exerted oncogenic effects through activation of the PI3K/Akt signaling pathway. <b>Conclusions:</b> PSMB9 promotes the malignant progression of colorectal cancer by regulating the PI3K/Akt signaling pathway.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"24"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796242","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":"Stage-Specific Regulation of Ubiquitination Modifications and Prospects for Targeted Therapy in Triple-Negative Breast Cancer.","authors":"Yongpan Wang, Weiqiang Huang, Qizhuan Lin, Helei Cai, Fengjin Dai, Haiqing Gu, Shunyan Yu, Libo Jin, Renyi Peng","doi":"10.32604/or.2026.080113","DOIUrl":"10.32604/or.2026.080113","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by poor clinical outcomes. Owing to the absence of estrogen receptors, progesterone receptors, and Human Epidermal Growth Factor Receptor 2 (HER2) expression, TNBC shows limited responsiveness to conventional endocrine and targeted therapies. This subtype exhibits strong heterogeneity, a high propensity for metastasis, and a tendency to develop acquired drug resistance. Its survival and progression largely rely on non-classical signaling pathways, including Epidermal growth factor receptor (EGFR), Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT), and Notch, which collectively impose substantial challenges to clinical management. In recent years, protein post-translational modifications-particularly ubiquitination and ubiquitin-like modifications-have emerged as key mechanisms governing TNBC malignant progression. This review systematically summarizes the stage-specific regulatory roles of ubiquitination during TNBC initiation, progression, and therapeutic resistance. These mechanisms include modulation of tumor stemness, epithelial-mesenchymal transition, DNA damage repair, ferroptosis, and immune evasion through the regulation of critical proteins such as Toll-like receptor 4/Nuclear factor kappa-B (TLR4/NF-κB), Twist family bHLH transcription factor 1 (TWIST1), Poly (ADP-Ribose) Polymerase 1 (PARP1), Programmed death-ligand 1 (PD-L1), and Glutathione Peroxidase 4 (GPX4). In addition, ubiquitin-like modifications (including small ubiquitin-like modifier (SUMOylation), Neural precursor cell expressed developmentally downregulated protein 8 (NEDDylation), and Interferon-stimulated gene (ISGylation)) function synergistically in maintaining genome stability, transcriptional regulation, and immunological processes. Furthermore, this review highlights the translational potential of targeting ubiquitination pathways in TNBC, covering the applications, advantages, and limitations of immune checkpoint inhibitors, Poly ADP-ribose polymerase (PARP) inhibitors, antibody-drug conjugates, and combination treatment strategies. Finally, it outlines future research directions, such as developing a TNBC-specific ubiquitinome landscape, creating highly selective E3 ligase or deubiquitinase inhibitors, and integrating multi-omics with artificial intelligence technologies. These advances are expected to provide a theoretical foundation and translational insights for precision interventions targeting protein homeostasis in TNBC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 9","pages":"7"},"PeriodicalIF":4.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796272","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}