OncoTargets and therapy最新文献

{"title":"Immunotherapy Resistance and Therapeutic Strategies in PD-L1 High Expression Non-Small Cell Lung Cancer.","authors":"Jianhua Liu, Yin Cai, Jiang Liu, Dadong Chen, Xiang Wu","doi":"10.2147/OTT.S539978","DOIUrl":"10.2147/OTT.S539978","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and high programmed death-ligand 1 (PD-L1) expression (≥50%) is a key biomarker for predicting clinical benefit from immune checkpoint inhibitors (ICIs). This therapy has substantially improved long-term survival rates, with a five-year survival rate exceeding 25%. Nevertheless, primary or acquired resistance occurs in 30-40% of PD-L1-high patients. This resistance arises from multifactorial mechanisms involving tumor-intrinsic adaptations, immune microenvironment reprogramming, and extrinsic immunosuppressive signals. In this review, we systematically dissect the biological and clinical drivers of ICIs resistance in PD-L1-high NSCLC and explore emerging strategies to overcome these barriers, including novel combinatorial approaches and biomarker-guided therapies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"953-966"},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001015","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":"CD93: A Promising NETs-Related Biomarker for Diagnosis and Therapy in Actinic Keratosis.","authors":"Guolin Ke, Tao Yuan, Chen Wu, Min Gao","doi":"10.2147/OTT.S539790","DOIUrl":"10.2147/OTT.S539790","url":null,"abstract":"<p><strong>Background: </strong>Actinic keratosis (AK), a UV-induced precancerous skin condition potentially progressing to cutaneous squamous cell carcinoma (cSCC) with undefined mechanisms, was analyzed for neutrophil extracellular traps (NETs)-related biomarkers to identify key clinical targets.</p><p><strong>Methods: </strong>Transcriptomic profiles of AK retrieved from the GEO database were analyzed using the \"limma\" package to screen differentially expressed genes (DEGs), which were intersected with a curated NETs-related gene set to extract differentially expressed NETs-related genes (DE-NRGs). Functional enrichment analyses via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations identified enriched biological processes and pathways. Diagnostic biomarkers were screened using LASSO regression, random forest (RF), and Support Vector Machine Recursive Feature Elimination (SVM-RFE), with performance assessed by receiver operating characteristic (ROC) curves. Clinical validation compared CD93-positive microvessel density (CD93-MVD) levels between 53 AK samples and normal skin controls. Single-sample gene set enrichment analysis (ssGSEA) evaluated immune cell infiltration and neutrophil-related pathway activity, while molecular docking screened potential CD93-targeting drugs.</p><p><strong>Results: </strong>Nine DE-NRGs were identified by comparing AK samples with controls. GO/KEGG enrichment highlighted neutrophil chemotaxis, migration, and IL-17 signaling pathways. LASSO, RF, and SVM-RFE selected CD93 as a key diagnostic biomarker, showing overexpression in training (GSE207744, AUC=0.863) and validation (GSE32628, AUC=0.956) datasets. Immunohistochemistry confirmed significantly higher CD93-MVD levels between AK and normal skin (p=5.36×10^-¹¹), with elevation in elderly patients (p=0.042), multifocal lesions (p=0.028), and with increasing severity (clinical: p=0.040; dermoscopic: p=0.007; pathological: p=2.3×10^-6). ssGSEA revealed increased immune cell infiltration and neutrophil pathway activity in AK. Molecular docking identified Gö6976 as a CD93 inhibitor (ΔG=-7.5 kcal/mol).</p><p><strong>Conclusion: </strong>Our study establishes CD93 as a key NETs-related biomarker in AK, mechanistically linking neutrophil-driven inflammation to angiogenesis. The CD93-Gö6976 interaction provides a translational basis for developing novel targeted therapies against AK.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"935-951"},"PeriodicalIF":2.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992972","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":"The Role of CELMoD Agents in Multiple Myeloma.","authors":"Niels W C J van de Donk, Nizar J Bahlis, Charlotte Pawlyn, Francesca Gay, Maria-Victoria Mateos, Katja Weisel, Sagar Lonial, Paul G Richardson","doi":"10.2147/OTT.S398118","DOIUrl":"10.2147/OTT.S398118","url":null,"abstract":"<p><p>Although recent decades have seen continued improvements in survival for patients with multiple myeloma, the disease remains largely incurable, and most patients will experience relapse and/or become refractory to treatment. There thus remains an urgent unmet need for novel treatments, particularly for those patients with relapsed or refractory multiple myeloma. Novel treatment modalities, such as targeted protein degradation, have attracted particular interest due to their ability to expand the range of druggable protein targets in myeloma cells. Iberdomide (CC-220) and mezigdomide (CC-92480) are promising oral CELMoD™ agents currently being evaluated for the treatment of patients with multiple myeloma. Preclinical data from lenalidomide- and pomalidomide-resistant cell lines and mouse models suggest that iberdomide and mezigdomide have the potential to provide therapeutic benefit even in patients who are refractory to lenalidomide and pomalidomide. The optimized specificity, potency, and safety profile of iberdomide and mezigdomide supports their clinical use and aligns with the need for longer durations of a well-tolerated oral CELMoD agent with synergistic combinability with other immune approaches (such as anti-CD38 monoclonal antibodies) and proteasome inhibitors (such as bortezomib and carfilzomib). Although neither iberdomide or mezigdomide has yet received regulatory approval for the treatment of multiple myeloma, based on their mechanism of action and the data available to date, we propose that both drugs may be attractive options for the treatment of patients with relapsed or refractory multiple myeloma; based on their efficacy and safety profiles, iberdomide is likely better suited for use in newly diagnosed, first relapse, or maintenance settings, whereas mezigdomide may also be better suited for use in patients with early relapse or a greater number of prior antimyeloma treatments. Iberdomide and mezigdomide are currently being evaluated for the treatment of patients with multiple myeloma in several trials, and results so far are promising.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"921-933"},"PeriodicalIF":2.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992920","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":"Crosstalk Between Immunity and Oncogenes Within the Tumor Microenvironment of HPV-Associated Cervical Squamous Cell Carcinoma.","authors":"Reham M Alahmadi, Halah Z Al Rawi, Maaweya Awadalla, Bashayer Saeed, Basma Abdelazeem, Huda M Alshanbari, Bandar Alosaimi","doi":"10.2147/OTT.S537872","DOIUrl":"10.2147/OTT.S537872","url":null,"abstract":"<p><strong>Introduction: </strong>Every two minutes, a woman dies from cervical cancer, which is considered the fourth most common cancer among women worldwide. The dynamic interplay between tumor inflammation, immune crosstalk, oncogenes, and tumor suppressor genes plays a crucial role in tumor development and progression.</p><p><strong>Methods: </strong>Using clinical and integrated bioinformatics, the mRNA expression pattern of 168 immune and tumor-related genes in the tumor microenvironment (TME) of HPV-positive cervical squamous cell carcinoma (CSCC) was analyzed.</p><p><strong>Results: </strong>The study identified 94 DEGs, of which 55 genes were remarkably upregulated, including CASP8, ZHX2, BCL2L1, CTNNB1, RB1, BAX, CD274, CCL20, FOXP3, and CCL18. The top three-fold changes were associated with CASP8, ZHX2, and BCL2L1, respectively. In contrast, downregulation was discovered for 39 genes associated with immunity, regulation of cell cycle, and DNA damage response (HRAS, CCND1, ATM, CXCR1, and MIF). Gene-gene interaction and correlation analysis showed positive correlations, including RB1 and CASP8, RB1 and BCL2L1, and CCL20 with CCL18. Notably, six genes exhibited increased expression and showed a strong correlation with enhanced overall survival (OS) and disease-free survival (DFS), indicating their potential utility as prognostic biomarkers. Upregulated genes were positively associated with various immune cells, including B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells. Functional enrichment analysis revealed involvement in cancer-related processes, inflammatory responses, and cell migration, with key pathways linked to cytokine signaling and chemokine receptor interactions.</p><p><strong>Discussion: </strong>Through the integration of clinical, experimental, and computational analyses, potential therapeutic targets and prognostic biomarkers were identified that may help improve clinical outcomes. Future studies should focus on the functional assays of identified genes both in vitro and in vivo.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"899-920"},"PeriodicalIF":2.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963740","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":"Migrasome-Related Prognostic Genes in Gastric Cancer: A Transcriptomic and Immunotherapeutic Analysis.","authors":"Wei Qiu, Ke Zhang, Wei Hu, DongSheng Liu","doi":"10.2147/OTT.S528050","DOIUrl":"10.2147/OTT.S528050","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide, characterized by complex pathogenesis and poor prognosis. Migrasomes, as newly discovered organelles, play crucial roles in tumor microenvironment modulation and immune regulation. However, their specific mechanisms in GC remain largely unknown.</p><p><strong>Methods: </strong>This study integrated GC transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases with 35 migrasome-related genes (MRGs) to identify differentially expressed genes through bioinformatics analysis. A prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression, and subsequent analyses were conducted through gene set enrichment analysis (GSEA), immune infiltration assessment, and drug sensitivity evaluation. Key gene expressions were further verified in clinical samples via reverse transcription quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>Eight migrasome-related prognostic genes were identified (BMP1, CPQ, PDGFD, TSPAN5, TSPAN7, TGFB2, WNT11, and LEFTY1). The developed risk-scoring model demonstrated predictive performance in both training and validation cohorts (area under the curve (AUC) > 0.6). Functional analysis revealed significant enrichment of these genes in key pathways, particularly the TGF-β signaling pathway. Immune profiling showed distinct microenvironment features in high-risk groups, along with differential sensitivity to specific chemotherapeutic agents (eg, BMS-754807). Experimental validation confirmed significant upregulation of BMP1 (p < 0.05), LEFTY1 (p < 0.05), and TGFB2 (p < 0.01), along with downregulation of TSPAN5 in GC tissues (p < 0.001).</p><p><strong>Conclusion: </strong>This study reveals the prognostic value of eight genes related to migrators in GC. The established risk model provides novel molecular markers and potential therapeutic targets for personalized GC treatment. These findings offer critical insights for understanding GC pathogenesis and developing innovative treatment strategies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"873-897"},"PeriodicalIF":2.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874335","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":"Innovative Biomarkers for Diagnosing Malignant Ascites in Liver Cancer.","authors":"Yan Zhang, Jing Wu, Huaizhong Cui, Xiaojing Zhang, Lingyan He, Kailong Gu, Aifang Xu","doi":"10.2147/OTT.S527224","DOIUrl":"10.2147/OTT.S527224","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer ranks among the most prevalent and lethal malignancies worldwide, with metastatic malignant ascites being a common complication. This study seeks to assess the diagnostic significance of high fluorescent cells (HFCs), biochemical and tumor markers in predicting the development of metastatic malignant ascites in patients with liver cancer.</p><p><strong>Methods: </strong>We collected ascites samples from 266 patients diagnosed with liver cancer. HFC were analyzed using the BF mode of the BC-7500 hematology analyzer, assessing both relative counts (HF-BF%) and absolute counts (HF-BF#). Additionally, biochemical and tumor markers were evaluated in serum and ascites. The diagnostic accuracy of these indicators, both individually and in combination, was assessed using receiver operating characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>The malignant ascites group exhibited significantly higher levels of HF-BF%, cancer ratio 2 (Ratio2, ascites LDH: ascites ADA Ratio), and neuron-specific enolase (NSE) compared to the benign group, identifying these markers as independent risk factors for malignant ascites in liver cancer patients. Ratio2 demonstrated limited diagnostic value for malignant ascites, with an area under the curve (AUC) of 0.614. In contrast, HF-BF% and NSE showed moderate diagnostic capabilities, with AUCs of 0.760 and 0.700, respectively. The combined assessment of all three indicators yielded a high diagnostic capability, with an AUC of 0.824. The critical values for NSE, HF-BF%, and Ratio2 were 11.42 U/mL, 4.35/100 WBC, and 32.82%, respectively.</p><p><strong>Conclusion: </strong>The combined evaluation of HF-BF%, Ratio2, and NSE serves as a valuable indicator for predicting the occurrence of metastatic malignant ascites in liver cancer patients.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"865-872"},"PeriodicalIF":2.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874334","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":"Upregulation of SHIP2 Participates in the Development of Breast Cancer via Promoting Wnt/β-Catenin Signaling [Retraction].","authors":"","doi":"10.2147/OTT.S558484","DOIUrl":"https://doi.org/10.2147/OTT.S558484","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/OTT.S223422.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"863-864"},"PeriodicalIF":2.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12338311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822166","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":"The Expression and Clinical Significance of ALDOA in Breast Cancer.","authors":"Yuning Dai, Yong Yang, Xiaohua Li, Guojian Shi, Ting Ni, Qilu Zhu, Qin He, Aoni Hu, Hao Jiang, Jianxia Liu, Ting Lu, Jie Sun, Enqiao Yu, Liang Sun","doi":"10.2147/OTT.S518473","DOIUrl":"10.2147/OTT.S518473","url":null,"abstract":"<p><strong>Background: </strong>Several malignant tumors have been shown to overexpress aldolase A (ALDOA), a crucial enzyme in the glycolytic cycle. Though, it is still unknown how ALDOA contributes to breast cancer (BC).</p><p><strong>Methods: </strong>Using GEPIA, TIMER, UALCAN, BC-GenExMiner v5.1 database, and immunohistochemistry on 96 BC patients, the expression of ALDOA was investigated. The correlation between ALDOA expression and the prognosis was evaluated by employing the Kaplan-Meier (KM) plotter in breast cancer patients.</p><p><strong>Results: </strong>The expression of ALDOA mRNA was higher in BC compared to the normal tissues. Certain subtypes of BC showed higher ALDOA expression, including micropapillary, luminal B, non-basal-like, non-triple negative breast cancer (TNBC), and luminal androgen receptor (LAR). Overexpression of ALDOA was related to the presence of lymph node metastasis (LNM), older age, high Ki67 expression, estrogen receptor (ER) and progesterone receptor (PR) positivity, and advanced Scarff-Bloom-Richardson (SBR) and Nottingham Prognostic Index (NPI) grades, while decreased ALDOA mRNA levels were observed in TNBC and basal-like BC. KM plotter showed that higher ALDOA mRNA levels predicted worse overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) overall. However, in BC patients with LNM, higher ALDOA levels correlated to better DMFS.</p><p><strong>Conclusion: </strong>ALDOA was a crucial prognostic factor required for BC advancement, indicating a possible target for BC treatment.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"845-862"},"PeriodicalIF":2.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817163","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":"Immune-Checkpoint Inhibitors in Lung Neuroendocrine Tumors - A Systematic Review and Meta-Analysis.","authors":"Rita Carrilho Pichel, Lavinia Benini, Marco Romelli, Sara Gandini, Lorenzo Gervaso, Monica Valente, Maria João De Sousa, Alexandra Araújo, António Araújo, Anna Maria Di Giacomo, Nicola Fazio","doi":"10.2147/OTT.S515194","DOIUrl":"10.2147/OTT.S515194","url":null,"abstract":"<p><p>Lung neuroendocrine tumors (NETs) are well-differentiated neuroendocrine neoplasms of lung origin, including typical and atypical carcinoids (ACs). Therapeutic options for this rare disease are limited in daily clinical practice. Immune-checkpoint inhibitors (ICIs) are under clinical investigation. Here, we report a systematic reappraisal about ICIs results in lung NETs. We reviewed articles on observational or interventional studies that reported efficacy data of ICIs in lung NETs. Case reports and studies with insufficient data were excluded from the analysis. We searched the electronic databases Medline, Embase, Web of Science, and Cochrane Library up to May 2024. Two investigators independently screened the identified records and assessed studies quality. We summarized the results descriptively and in a meta-analysis of ORR according to the type of intervention. The search retrieved 1344 records. After selection, we included 11 studies in the meta-analysis of ORR, with a total of 128 adult patients with lung NET (25% ACs) that were progressing after at least one line of systemic therapy, including treatment with somatostatin analogs. Ten studies were Phase II, and 1 study was phase Ib. The summary ORR was 14.7% (95% CI, 5.8-32.2), 44.4% (27.2-63.1) for ACs. Subgroup analysis by intervention types showed a trend for lower ORR of lung NETs treated with ICI monotherapy (ORR: 2.7%; 0.0-63.7) compared with combinations (p-value: 0.056). The combination of temozolomide plus nivolumab showed the highest ORR (66.7%; 33.3-88.9). The median OS (reported in 2 studies) was not reached. Safety was consistent with historical data of ICIs. Our work suggests that ICIs are a promising treatment for patients with lung NETs, especially ACs, and warrant further investigation in more focused studies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"833-843"},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794950","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":"Advances in ORMDL Research in Malignant Tumors: A Review.","authors":"Hao Wang, Zhongquan Yi, Song Yan, Yihao Wang, Weisong Zhang, Rongqi Guo, Yangyang Li, Rui Wang, Heng Li, Xia Li, JianXiang Song","doi":"10.2147/OTT.S537194","DOIUrl":"10.2147/OTT.S537194","url":null,"abstract":"<p><p>ORMDL proteins (ORMDL1, ORMDL2, ORMDL3) are transmembrane proteins in the endoplasmic reticulum (ER) that regulate sphingolipid metabolism, maintain ER homeostasis, and modulate cellular stress responses. They influence cell proliferation, apoptosis, and metabolic balance. Recent studies have highlighted the altered expression and function of ORMDL proteins in various tumors, including breast cancer, DLBCL, colorectal cancer, and lung cancer. ORMDLs negatively regulate serine palmitoyltransferase (SPT), affecting ceramide and sphingolipid metabolism, which plays a key role in tumor cell proliferation, invasiveness, and resistance to therapy. The dysregulation of ORMDL expression may disrupt sphingolipid metabolism, trigger ER stress, and impair autophagy. Investigating ORMDL functions in cancer could lead to novel insights into tumor development and progression. ORMDL expression may serve as a potential biomarker for cancer diagnosis, prognosis, and therapeutic response prediction. Targeting ORMDL or its metabolic networks offers promising strategies for cancer therapy. Although research on ORMDLs is still in its early stages, further studies are needed to explore their roles in the tumor microenvironment, interactions with the immune system, and applications in personalized medicine. A deeper understanding of ORMDL proteins will enhance tumor diagnosis, treatment, and the development of new therapeutic approaches.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"821-832"},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775913","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}