OncoTargets and therapy最新文献

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Glycolysis-Driven Immune Evasion in Microsatellite Instability-High Colorectal Cancer: An Integrated Single-Cell and Spatial Transcriptomics Study. 微卫星不稳定性高的结直肠癌中糖酵解驱动的免疫逃避:一项综合单细胞和空间转录组学研究。
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S538018
Chenchen Li, Peicong Cai, Hengda Zeng, Jianxia Li, Huabin Hu, Jianwei Zhang, Zehua Wu, Ge Qin, Yanhong Deng
{"title":"Glycolysis-Driven Immune Evasion in Microsatellite Instability-High Colorectal Cancer: An Integrated Single-Cell and Spatial Transcriptomics Study.","authors":"Chenchen Li, Peicong Cai, Hengda Zeng, Jianxia Li, Huabin Hu, Jianwei Zhang, Zehua Wu, Ge Qin, Yanhong Deng","doi":"10.2147/OTT.S538018","DOIUrl":"10.2147/OTT.S538018","url":null,"abstract":"<p><strong>Purpose: </strong>Microsatellite instability-high colorectal cancer is characterized by hypermutated genomes and high neoantigen loads, yet a significant proportion of patients exhibit resistance to immune checkpoint blockade. This study aims to investigate tumor cell functional heterogeneity and its role in immune evasion.</p><p><strong>Patients and methods: </strong>We integrated single-cell RNA sequencing, spatial transcriptomics, and bulk RNA sequencing from microsatellite instability-high colorectal cancer patients. After quality control, normalization, and clustering, malignant epithelial subpopulations were identified through copy number variation analysis and non-negative matrix factorization. Functional characterization employed gene set enrichment analysis. Spatial transcriptomics clarified immune cell and tumor subpopulation localization, and survival analyses assessed prognostic implications.</p><p><strong>Results: </strong>We identified a glycolysis-enriched tumor subpopulation (MP2) that co-localized with immunosuppressive niches marked by Treg accumulation, effector T-cell depletion, and FOLR2+ tumor-associated macrophages. MP2-high tumors were associated with immune checkpoint blockade resistance and poor prognosis. Mechanistically, MP2 cells secreted lactate, promoting Treg differentiation and macrophage polarization toward an immunosuppressive phenotype. Spatial transcriptomics revealed the precise organization of these lactate-rich, immune-excluded niches within tumors.</p><p><strong>Conclusion: </strong>These findings establish tumor cell-intrinsic glycolysis as a key driver of immune evasion in microsatellite instability-high colorectal cancer and propose metabolic targeting as a strategy to overcome immune checkpoint blockade resistance.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"1027-1042"},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131486","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}
引用次数: 0
Can Epithelial-Myoepithelial Carcinoma of the Breast Benefit from TROP2 Antibody-Drug Conjugate? TROP2抗体-药物偶联物能治疗乳腺上皮-肌上皮癌吗?
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-09-12 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S540295
Qing Zhao, Xiao Luo, Hua Xing, Chengwei Jiang, Jingchao Ma, Lu Tang
{"title":"Can Epithelial-Myoepithelial Carcinoma of the Breast Benefit from TROP2 Antibody-Drug Conjugate?","authors":"Qing Zhao, Xiao Luo, Hua Xing, Chengwei Jiang, Jingchao Ma, Lu Tang","doi":"10.2147/OTT.S540295","DOIUrl":"10.2147/OTT.S540295","url":null,"abstract":"<p><p>Epithelial-myoepithelial carcinoma (EMC) of the breast is a rare biphasic tumor composed of intermixed malignant epithelial and myoepithelial components. Breast epithelial myoepithelial carcinoma lacks therapeutic strategies due to its rarity, and currently local treatment is still the main treatment. Herein we report an epithelial-myoepithelial carcinoma of the breast in a 33-year-old woman undergoing breast conserving surgery, sentinel lymph node biopsy, adjuvant chemotherapy and radiotherapy, with rapid liver and lung metastasis. After radiofrequency ablation therapy for metastatic lesions, vinorelbine plus cisplatin and TROP2 antibody-drug conjugate (ADC) treatment were given successively. After a brief improvement, drug resistance developed and the disease progressed. The patient died with the PFS 5.6 months.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"1013-1025"},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081275","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}
引用次数: 0
The Immunomodulatory Activity of Thymosin Alpha 1 on Tumor Cell Lines and Distinct Immune Cell Subsets. 胸腺素α 1对肿瘤细胞系和不同免疫细胞亚群的免疫调节活性。
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-09-10 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S527785
Laura Solmonese, Maria Fortunata Lofiego, Carolina Fazio, Francesco Marzani, Francesca Piazzini, Emma Bello, Fabrizio Celesti, Gianluca Giacobini, Xiaohui Wang, Michele Maio, Sandra Coral, Anna Maria Di Giacomo, Alessia Covre
{"title":"The Immunomodulatory Activity of Thymosin Alpha 1 on Tumor Cell Lines and Distinct Immune Cell Subsets.","authors":"Laura Solmonese, Maria Fortunata Lofiego, Carolina Fazio, Francesco Marzani, Francesca Piazzini, Emma Bello, Fabrizio Celesti, Gianluca Giacobini, Xiaohui Wang, Michele Maio, Sandra Coral, Anna Maria Di Giacomo, Alessia Covre","doi":"10.2147/OTT.S527785","DOIUrl":"10.2147/OTT.S527785","url":null,"abstract":"<p><strong>Background: </strong>The immune-balancing role of thymosin alpha 1 (Tα1) is well-recognized in contexts of immune dysregulation. Within the anti-tumor context, Tα1 demonstrated to act as an immune-enhancer, with potential roles in immunotherapy-based treatments. However, Tα1 immunomodulatory potential on tumor cells is poorly understood. Additionally, Tα1 pleiotropic effects on immune cells require in-depth investigations to unravel its specific impact on different immune cell populations. Thus, we first aimed to investigate whether Tα1 treatments influenced the transcriptional immune profile of various cancer cell lines. Alongside, CD4<sup>+</sup> T, CD8<sup>+</sup> T, B, and natural killer cells from healthy donors (HDs) were treated individually with Tα1, to assess its direct effects on each immune cell population.</p><p><strong>Methods: </strong>Cutaneous melanoma, glioblastoma, and pleural mesothelioma cell lines and HD immune cell subsets were treated with Tα1 for 48 hours. Total RNA was subsequently isolated, and gene expression profiles were analyzed by the nCounter<sup>®</sup> SPRINT Profiler. Genes with a log2ratio ≥0.58 and ≤-0.58 in Tα1-treated vs untreated cells were defined as differentially expressed (DEGs) and subsequently evaluated for the enrichment of Gene Ontology terms to identify biological processes potentially affected by Tα1 in tumor and immune cells.</p><p><strong>Results: </strong>Tα1 minimally changed cancer cell DEGs and immune-related biological processes, suggesting a comprehensive lack of transcriptional immunomodulatory potential on the tumor counterpart. Conversely, Tα1 exhibited to directly affect the proliferation and/or transcription processes of each studied immune cell subset, with the greatest transcriptional impact observed for activated CD8<sup>+</sup> T cells, crucial players in anti-tumor immunity.</p><p><strong>Conclusion: </strong>Our findings question the tumor immunomodulatory properties of Tα1, simultaneously underscoring the importance of further investigating Tα1 influence on specific immune cell subsets in the periphery or within the tumor microenvironment of cancer patients. This would contribute to understand Tα1 potential in immunotherapy-based combination strategies, within the anti-tumor setting.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"995-1012"},"PeriodicalIF":2.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069958","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}
引用次数: 0
The Dual Role of RBBP7 in Esophageal Squamous Cell Carcinoma: Cell Context-Dependent Impacts on Proliferation and Radiosensitivity. RBBP7在食管鳞状细胞癌中的双重作用:细胞环境依赖性对增殖和放射敏感性的影响
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-09-04 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S535750
Yafen Li, Shuai Lu, Hui Yao, Genbao Zhu, Hao Liu, Zhiyu Ma, Heng Tang
{"title":"The Dual Role of RBBP7 in Esophageal Squamous Cell Carcinoma: Cell Context-Dependent Impacts on Proliferation and Radiosensitivity.","authors":"Yafen Li, Shuai Lu, Hui Yao, Genbao Zhu, Hao Liu, Zhiyu Ma, Heng Tang","doi":"10.2147/OTT.S535750","DOIUrl":"10.2147/OTT.S535750","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy resistance contributes to poor prognosis in esophageal squamous cell carcinoma (ESCC). Retinoblastoma-binding protein 7 (RBBP7) is a nuclear protein, and it can promote or inhibit tumor progression in cancer, but its function in ESCC cells and impact on radiosensitivity remains unclear.</p><p><strong>Methods: </strong>RBBP7 expression in cancer was analyzed using an online website. The expression levels of RBBP7 in ESCC cells (TE-1 and KYSE-150) and tissues were tested. Cells were subjected to RBBP7 gene silencing and irradiation (IR). Assays included CCK-8, clonogenic survival, flow cytometry (apoptosis/cell cycle), ROS detection, and Western blotting for DNA damage (γ-H2AX) and STAT3 signaling. Additionally, pathological tissue specimens and clinical data from ESCC patients were used to explore the expression of RBBP7.and its relationship with the clinical parameters of patients.</p><p><strong>Results: </strong>RBBP7 was overexpressed in malignant tumors. In ESCC cells, the mRNA and protein of RBBP7 were also highly expressed. After silencing RBBP7 combined with IR treatment, contradictory effects were observed between cell lines: In well-differentiated TE-1 cells, RBBP7 knockdown suppressed proliferation, enhanced radiosensitivity (SER=1.370), increased ROS/DNA damage (γ-H2AX), promoted apoptosis, and reduced STAT3 activation (possibly through STAT3 signaling). In poorly-differentiated KYSE-150 cells, knockdown promoted proliferation, decreased radiosensitivity (SER=0.775), reduced apoptosis, and increased p-STAT3. In addition, knockdown caused S-phase arrest (TE-1) versus G0/G1 arrest (KYSE-150), with divergent CDK4/Cyclin D1 regulation. Clinical analysis confirmed RBBP7 positivity correlated with tumor differentiation, TNM stage, and radiotherapy method.</p><p><strong>Conclusion: </strong>RBBP7 is highly expressed in ESCC, and it exerts cell context-dependent dual roles in ESCC, leading to differences in cellular radiosensitivity, possibly mediated through STAT3 signaling. This dichotomy highlights its potential as a differentiation status-specific therapeutic target.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"979-994"},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040924","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}
引用次数: 0
Mi-Lnc70 Regulates the Progression of Murine Pancreatic β-Cell Line and Affects the Synthesis of Insulin and Glucagon. Mi-Lnc70调节小鼠胰腺β-细胞系的生长及胰岛素和胰高血糖素的合成。
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S523599
Wen Yuan, Dongxue Sun, Jing Wang, Yongli Yue, Xueling Li
{"title":"Mi-Lnc70 Regulates the Progression of Murine Pancreatic β-Cell Line and Affects the Synthesis of Insulin and Glucagon.","authors":"Wen Yuan, Dongxue Sun, Jing Wang, Yongli Yue, Xueling Li","doi":"10.2147/OTT.S523599","DOIUrl":"10.2147/OTT.S523599","url":null,"abstract":"<p><strong>Background: </strong>Insulinoma, the most common type of pancreatic endocrine tumor, frequently induces hypoglycemia due to persistent hyperinsulinemia. Although Mi-Lnc70 expression progressively increases during pancreatic maturation in mice, the biological role of Mi-Lnc70 in pancreatic β cells remains elusive.</p><p><strong>Aim: </strong>This study was designed to investigate the role of LncRNA-Mi-Lnc70 in the mouse pancreatic β-cell line MIN6.</p><p><strong>Methods: </strong>We performed quantitative real-time PCR, cell counting kit-8 (CCK-8) assay, flow cytometry, transwell assay, wound healing assay, immunofluorescence staining, and Western blotting.</p><p><strong>Results: </strong>The expression of Mi-Lnc70 was markedly elevated in mouse pancreatic β-cells (MIN6) compared to normal cells. Knockdown of Mi-Lnc70 markedly suppressed the proliferation, migration, and invasion capabilities of MIN6 cells but induced cell apoptosis and triggered G2/M phase cell cycle arrest. Moreover, Mi-Lnc70 knockdown influenced the expression profiles of pancreas-related lncRNAs and miRNAs and decreased the expression of islet-related genes and reduced the protein synthesis of INSULIN, GLUCAGON, and PDX1.</p><p><strong>Conclusion: </strong>Mi-Lnc70 plays an important role in the proliferation, migration, and endocrine-related gene expression in pancreatic MIN6 cells, particularly in the synthesis of PDX1, INSULIN, and GLUCAGON.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"967-978"},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030207","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}
引用次数: 0
Immunotherapy Resistance and Therapeutic Strategies in PD-L1 High Expression Non-Small Cell Lung Cancer. PD-L1高表达非小细胞肺癌的免疫耐药及治疗策略
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-08-29 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S539978
Jianhua Liu, Yin Cai, Jiang Liu, Dadong Chen, Xiang Wu
{"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}
引用次数: 0
CD93: A Promising NETs-Related Biomarker for Diagnosis and Therapy in Actinic Keratosis. CD93:光化性角化病诊断和治疗的有前途的nets相关生物标志物。
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-08-27 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S539790
Guolin Ke, Tao Yuan, Chen Wu, Min Gao
{"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<sup>-</sup>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<sup>-6</sup>). 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}
引用次数: 0
The Role of CELMoD Agents in Multiple Myeloma. CELMoD制剂在多发性骨髓瘤中的作用。
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-08-27 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S398118
Niels W C J van de Donk, Nizar J Bahlis, Charlotte Pawlyn, Francesca Gay, Maria-Victoria Mateos, Katja Weisel, Sagar Lonial, Paul G Richardson
{"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}
引用次数: 0
Crosstalk Between Immunity and Oncogenes Within the Tumor Microenvironment of HPV-Associated Cervical Squamous Cell Carcinoma. hpv相关宫颈鳞状细胞癌肿瘤微环境中免疫与癌基因间的串扰
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-08-15 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S537872
Reham M Alahmadi, Halah Z Al Rawi, Maaweya Awadalla, Bashayer Saeed, Basma Abdelazeem, Huda M Alshanbari, Bandar Alosaimi
{"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}
引用次数: 0
Migrasome-Related Prognostic Genes in Gastric Cancer: A Transcriptomic and Immunotherapeutic Analysis. 胃癌中偏头痛相关预后基因:转录组学和免疫治疗分析。
IF 2.8 4区 医学
OncoTargets and therapy Pub Date : 2025-08-13 eCollection Date: 2025-01-01 DOI: 10.2147/OTT.S528050
Wei Qiu, Ke Zhang, Wei Hu, DongSheng Liu
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