Journal of Cancer最新文献

{"title":"Epigenetic regulation espeically histone modifications in breast cancer: A viable and emerging targeted therapeutic strategy.","authors":"Yibing Zhou, Haotian Liu, Weimin Hong, Haotian Su, Yuxiao Mu, Yijie Cheng, Chaoshen Wu, Xuli Meng, Da Qian","doi":"10.7150/jca.119306","DOIUrl":"10.7150/jca.119306","url":null,"abstract":"<p><p>Epigenetic regulation, encompassing DNA methylation, histone modifications, and non-coding RNA activities, is a crucial mechanism through which gene expression is modified without corresponding changes in genomic DNA sequences. Dysregulation of these mechanisms can lead to histone and DNA modifications that either suppress or enhance the expression of disease progression-related genes. Among these regulatory processes, histone modifications are particularly significant, as they contribute to genomic stability, DNA repair, and chromatin dynamics, all of which influence breast cancer initiation and progression. This review offers a detailed analysis of the current state of research centered on epigenetic regulatory factors, with a particular focus on the role that histone modifications play in the treatment of breast cancer. It also examines the interplay between epigenetic modifications and the effectiveness of radiotherapy and chemotherapy when treating breast cancer. Lastly, this article explores the potential of epigenetic regulatory factors as viable targets for the future design of new anticancer therapies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"4037-4046"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Bowel Disease Mediates the Causal Relationship Between Gut Microbiota and Colorectal Cancer: Identification of Therapeutic Targets and Predictive Modeling.","authors":"Jin-Bei Wang, Zhen-Guo Wu, Guan-Wei Bi, Yu Li, Zhi-Wen Yao, Yan-Bo Yu","doi":"10.7150/jca.114687","DOIUrl":"10.7150/jca.114687","url":null,"abstract":"<p><p><b>Background:</b> Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Given its established associations with gut microbiota and inflammatory bowel disease (IBD), elucidating their relationships and developing predictive models are critical for early detection and therapy. <b>Methods:</b> Using Mendelian randomization (MR), we integrated data from the MiBioGen Consortium and multiple genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) associated with gut microbiota were mapped to genes, followed by gene selection via least absolute shrinkage and selection operator (LASSO) regression. Transcriptome analyses identified differential gene expressions and immune cell infiltration patterns. Six machine learning models were integrated through soft voting to predict CRC risk, validated by single-cell sequencing analysis. <b>Results:</b> Mediation MR identified 12 gut microbial taxa causally associated with CRC, mediated partially by IBD. SNP mapping and expression analysis highlighted eight CRC-associated genes, five of which (FAM120A, GBE1, MCM6, MSRA, ZDHHC4) were further underscored by drug target MR and summary-data-based MR (SMR). Transcriptomics implicated dysregulation in the neuroactive ligand-receptor interactions and the G2/M DNA checkpoint pathway. Immune infiltration analysis demonstrated elevated CD4⁺ T cells and M0 macrophages in the high-LASSO score group. Integrated machine learning models built using the five key genes achieved robust predictive performance. Single-cell sequencing analysis confirmed gene expression patterns. <b>Conclusion:</b> By integrating mediation MR, transcriptomics, and machine learning, this study demonstrated causal relationships between specific gut microbiota and CRC, with IBD as a mediator. We identified potential therapeutic targets and developed robust predictive models, providing crucial insights into the pathogenesis and clinical detection of CRC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"4008-4028"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nomogram for predicting axillary pathologic complete response after neoadjuvant systemic therapy in HER2 positive and triple negative breast cancer.","authors":"Zhendong Shi, Hanyan Zhu, Xiaoxing Bian, Xiaomin Qian, Jie Meng, Jin Zhang","doi":"10.7150/jca.118908","DOIUrl":"10.7150/jca.118908","url":null,"abstract":"<p><p><b>Purpose:</b> With the continuous improvement in the efficacy of neoadjuvant therapy (NAT), a significant proportion of breast cancer patients initially diagnosed with pathologically confirmed axillary lymph node metastasis (pN+) may achieve ypN0 status (no residual nodal metastasis) following NAT. This study aims to develop a predictive model for estimating the probability of achieving ypN0 status after NAT, thereby assisting surgeons in making optimal decisions regarding axillary management strategies. <b>Methods:</b> This retrospective study enrolled 671 patients diagnosed with pN+ at Tianjin Medical University Cancer Institute and Hospital between December 2018 and December 2022, all of whom completed NAT followed by surgical intervention. The cohort comprised 428 HER2-positive and 243 TNBC patients. Clinicopathological and ultrasound imaging data were systematically collected. Patients were stratified into training and validation sets at a 7:3 ratio based on admission dates. Univariate analysis was initially performed on the training set to identify potential factors associated with achieving ypN0 status post-NAT. Variables demonstrating statistical significance were subsequently incorporated into a multivariate logistic regression analysis to determine independent predictors. A predictive nomogram was then constructed using these independent factors via R software for visual interpretation of ypN0 probability. The predictive performance of the model was ultimately evaluated by generating receiver operating characteristic (ROC) curves to assess discriminative ability and calibration curves to quantify prediction accuracy, with further validation performed using the independent validation cohort. <b>Results:</b> In HER2 positive breast cancer patients, those exhibiting histological grade III, HER2 IHC 3+ expression, absence of lymphovascular invasion, clinical N1 stage, prominent and hypervascular tumor CDFI signal pre-NAT, and achievement of breast pathological complete response (bpCR) following NAT were significantly more likely to achieve ypN0 status. Conversely, among TNBC patients, independent predictors of post-NAT ypN0 achievement included histological grade III, taxane-platinum combination regimens, bpCR, dot-linear signals in axillary lymph nodes on post-NAT ultrasound, and minimal transverse diameter of node on final post-NAT ultrasound evaluation. <b>Conclusions:</b> This study established distinct predictive models for HER2-positive and TNBC cohorts with initial pN+ status to estimate the probability of achieving ypN0 following NAT. Both models demonstrated robust predictive performance through rigorous validation, providing clinicians with quantitative tools to optimize axillary management strategies and facilitate precision-based individualized treatment planning.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"3991-4007"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic alterations in triple-negative breast cancer and their clinical implications for diagnosis and therapy.","authors":"Eun-Jin Go, Ji Hoon Oh","doi":"10.7150/jca.119442","DOIUrl":"10.7150/jca.119442","url":null,"abstract":"<p><p>Breast cancer, including triple-negative breast cancer (TNBC), is the most commonly diagnosed cancer in women, with subtypes differing in treatment options and prognoses. In particular, TNBC, characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, is the most aggressive subtype, with limited treatment options, high metastatic rates, and poor survival outcomes. In recent years, epigenetic studies have emerged as a promising tool for analyzing gene expression and alterations in TNBC, providing potential insights into the development of novel therapeutic strategies. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNA (ncRNA)-mediated gene silencing, play a crucial role in the development and progression of TNBC. Research into these mechanisms holds significant promise for the development of personalized therapeutic approaches, potentially improving outcomes for TNBC patients. This review provides a comprehensive overview of recent advances in research on epigenetic alterations in TNBC, with an emphasis on potential clinical applications aimed at improving survival and quality of life in TNBC patients.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"4029-4036"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin Cancer: Epidemiology, Screening and Clinical Features of Acral Lentiginous Melanoma (ALM), Melanoma <i>In Situ</i> (MIS), Nodular Melanoma (NM) and Superficial Spreading Melanoma (SSM).","authors":"Chun-Te Lu, Teng-Li Lin, Arvind Mukundan, Riya Karmakar, Anusha Chandrasekar, Wen-Yen Chang, Hsiang-Chen Wang","doi":"10.7150/jca.116362","DOIUrl":"10.7150/jca.116362","url":null,"abstract":"<p><p>Melanoma, a highly aggressive form of skin cancer, presents considerable challenges in early detection and accurate diagnosis, particularly across its diverse subtypes such as acral lentiginous melanoma (ALM), melanoma <i>in situ</i> (MIS), nodular melanoma (NM), and superficial spreading melanoma (SSM). This study assesses the epidemiology, clinical characteristics, and screening techniques related to various melanoma subtypes, emphasizing their distinct features and risk factors. Moreover, the use of machine learning (ML) methodologies to categorize melanoma subtypes and the thorough examination of advancements in AI-based melanoma diagnosis, primarily emphasizing convolutional neural networks (CNN) and transfer learning approaches. Evaluate the efficacy of several deep learning models in classifying melanoma subtypes while addressing significant obstacles, including class imbalance and model generalization. Furthermore, it contemplates the integration of multimodal data, including genetic information and patient demographics, to enhance diagnostic accuracy. This comprehensive review assesses the epidemiology, clinical characteristics, and machine learning techniques utilized for the classification and detection of different melanoma subtypes, emphasizing recent advancements in AI-driven methods and their clinical significance.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"3972-3990"},"PeriodicalIF":3.2,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SREBP1-SCD1 enhanced MUFAs Biosynthesis drives Nutrient Deprived Pancreatic cancer cell Ferroptosis Resistance.","authors":"Zhengyang Zhang, Xiaojie Cai, Yi Gong, Aihua Gong, Xiang Liao, Jie Gao, Dongqing Wang","doi":"10.7150/jca.114356","DOIUrl":"10.7150/jca.114356","url":null,"abstract":"<p><p><b>Background:</b> As the most disastrous tumor microenvironment of pancreatic cancer, nutrient deprivation determined various cancer cell biology, especially the cell death resistance. Our objective is to elucidate the role of nutrient deprivation in ferroptosis resistance of pancreatic cancer cells and to explore potential therapeutic strategies to overcome it. <b>Methods:</b> To replicate the nutrient-deprived tumor microenvironment, pancreatic cancer cell lines (PANC1 and Patu8988T) were cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 2% fetal bovine serum (FBS). Ferroptosis was assessed by Cell Counting Kit-8 (CCK8), Malondialdehyde (MDA) assay, and C11 BODIPY staining. The signaling activity was assessed via western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. <b>Results:</b> Ferroptosis inducers promoted pancreatic cancer cell death could be significantly reversed under nutrient deprivation condition. Nutrient deprivation upregulated the expression of SREBP1 and SCD1, leading to increased intracellular levels of monounsaturated fatty acids (MUFAs). Genetic knockdown of SREBP1 or SCD1, as well as treatment with rapamycin (an mTOR inhibitor), reversed the nutrient deprivation induced increase in mature SREBP1 and SCD1 expression and restored lipid peroxidation both <i>in vitro</i> and <i>in vivo</i>. The synergistic application of sorafenib and rapamycin yielded a profoundly efficacious therapeutic outcome <i>in vivo</i>. <b>Conclusion:</b> Our findings demonstrate that nutrient-deprived pancreatic cancer cells adaptively enhance MUFA biosynthesis through the SREBP1-SCD1 axis, conferring resistance to ferroptosis. This resistance can be effectively overcome by combination therapy with sorafenib and rapamycin, offering a promising strategy to target the ferroptosis vulnerability shaped by the pancreatic tumor microenvironment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"3960-3971"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of the PARP inhibitor-related gene KANK3 for predicting prognosis and immunotherapeutic response in prostate cancer.","authors":"Yan Zhao, Qinghua Wang, Xin Qin, Wei Jiang, Haopeng Li, Mingming Xu, Xilei Li, Hanchu Ye, Juan Zhou, Xi Chen, Gang Wu","doi":"10.7150/jca.113546","DOIUrl":"10.7150/jca.113546","url":null,"abstract":"<p><p><b>Background:</b> Prostate cancer (PCa), a prevalent malignant neoplasm in men, has its biochemical recurrence-free survival (BCRFS) serving as a critical determinant for patient prognosis. PARP inhibitors have demonstrated potential therapeutic value in the management of PCa. Nevertheless, the precise influence exerted by their associated genes on BCRFS remains elusive. <b>Methods:</b> We selected the differentially expressed genes after treatment with olaparib and defined them as PARP inhibitor-related genes (PIRGs). Consensus clustering was employed to evaluate the relationships among different PIRGs clusters, prognosis, and the immune microenvironment. Univariate COX regression analysis was used to screen the prognosis-related PIRGs, which were then incorporated into multiple machine learning frameworks. The random forest algorithm with the highest C-index was chosen to construct a BCRFS prediction model. A prognostic nomogram was developed based on the risk score and clinical information, and the predictive performance of the model was assessed. <b>Results:</b> In C4 - 2B and LNCaP cell lines, 230 and 58 genes were differentially expressed, respectively. Consensus clustering results showed distinct survival prognoses and immune - infiltrated microenvironments among different groups. The random forest model had a high average C - index in both the training and validation sets. The prognostic model constructed in this study demonstrated a higher C-index compared to the prognostic models from previous studies. High - risk group patients had a poor immunotherapy response. A nomogram based on risk scores and clinical information accurately predicted PCa patients' BCRFS. Cell experiments revealed that KANK3 was downregulated in PCa and upregulated by olaparib treatment. KANK3 overexpression in PCa cell lines inhibited cell proliferation, migration, and invasion, suggesting its oncogenic role in PCa. <b>Conclusion:</b> Our study has described the correlations between PARP inhibitor-related genes and the immune landscape, recurrence after radical prostatectomy, as well as clinical characteristics. The risk score can improve the existing risk stratification system.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"3942-3959"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfidptosis-Associated CCNB2: A Prognostic Biomarker and Immune Microenvironment Modulator in Prostate Cancer.","authors":"Wei Jiang, Qinghua Wang, Juan Zhou, Yan Zhao, Xin Qin, Xilei Li, Haopeng Li, Licheng Wang, Gang Wu","doi":"10.7150/jca.112791","DOIUrl":"10.7150/jca.112791","url":null,"abstract":"<p><p><b>Background</b> Disulfidptosis, a newly recognized form of cell death activated by disulfide bond stress, differs from apoptosis, ferroptosis, cuproptosis, and pyroptosis. Understanding its role in prostate cancer is essential for developing tailored therapeutic approaches for managing this condition. Here, we establish the first disulfidptosis-based molecular subtyping framework for prostate cancer (PCa) and identify CCNB2 as a novel regulator of disulfidptosis, revealing its dual role in apoptosis activation and immune microenvironment remodeling. <b>Methods</b> We used consensus clustering to classify disulfidptosis into different subtypes and to study the unique characteristics linked to each one. We also developed a Dis score to measure the severity of each patient's subtype. We compared immune infiltration, pathway enrichment, and survival differences among the subtypes and revealed that the level of the score is significantly associated with the prognosis of PCa.Subsequently, we used Cytoscape software to further filter out hub genes and investigated how these genes influence the progression of PCa and their potential mechanisms through <i>in vitro</i> and <i>in vivo</i> experiments. <b>Results</b> We identified three molecular subtypes associated with disulfidptosis (Cluster A, B, C) and three gene subtypes (GeneCluster A, B, C). Each subtype exhibited a distinct prognosis, level of immune cell infiltration, and biological pathway activation. Notably, Cluster B and GeneCluster B, characterized by elevated disulfidptosis gene expression, were correlated with favorable prognosis. Additionally, we discovered that patients with higher scores exhibited lower tumor mutational burden (TMB) and improved prognosis. Finally, our experimental results confirmed that downregulation of CCNB2 expression promoted disulfidptosis in prostate cancer cells, thereby inhibiting their migration and proliferation capacities. <b>Conclusion</b> This study demonstrates that disulfidptosis can be utilized to stratify risk in patients with PCa. Furthermore, the CCNB2 gene emerges as a potential therapeutic target for prostate cancer by regulating disulfidptosis, thereby influencing the biological behaviors of PCa cells, including their proliferation and migration.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"3928-3941"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Plasma Protein Biomarkers and Drug Targets for Hematologic Malignancies by Proteome-wide Mendelian Randomization.","authors":"Tao Pan, Jiyue Zhang, Xiaomin Wang, Yuqin Song","doi":"10.7150/jca.115044","DOIUrl":"10.7150/jca.115044","url":null,"abstract":"<p><p><b>Background:</b> It has been reported that the proteome in blood was an important source for biomarker and therapeutic target discovery. However, up to now, few proteomes have been identified with the risk of hematologic malignancies. <b>Methods:</b> Genome-wide association studies (GWASs) including 3,083 plasma proteins are based on data from 54,219 people in the UK Biobank Pharma Proteomics Project (UKB-PPP) and 35,559 individuals from Iceland (deCODE). Genetic correlations with 33 hematologic malignancies were derived from the FinnGen cohort and the UK Biobank Data. Further studies, including Bayesian colocalization, protein-protein interaction assessment, pathway enrichment analysis, and drug target evaluation, were performed to enhance knowledge and identify prospective therapeutic targets for 33 hematologic cancers. <b>Results</b>: Our study indicated that 86 potential plasma proteins may have a substantial causal association with the incidence of 33 hematological tumors, such as BCL2, NFKB1, PARP1, and TNFRSF14. There are 18 proteins with strong evidence of genetic co-localization and 9 proteins with moderate support from colocalization analysis. Out of the 86 proteins, 51 have druggable targets, and 26 were identified as targets for current or prospective pharmaceuticals. <b>Conclusion</b>: Our research revealed numerous significant proteins linked to the likelihood of hematologic malignancies. It may elucidate protein-mediated processes of hematological tumors and provide prospective treatment options for individuals with these conditions.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"3917-3927"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Tri-Specific Immuno-Modulatory Antibody Combined with HDACi to Potentiate T Cell Activation and Anti-Tumor Efficacy.","authors":"Yidan Gou, Xiangfei Yuan, Dongmei Fan, Yuanyuan Yang, Hengjie Yuan","doi":"10.7150/jca.108922","DOIUrl":"10.7150/jca.108922","url":null,"abstract":"<p><p><b>Background:</b> Although blinatumomab, a bispecific T-cell engager, has exhibited promising clinical outcomes in the treatment of B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations due to CD19-negative relapse and an immunosuppressive phenotype. Epigenetic modulators have the potential to influence the tumor microenvironment (TME) and immune cycle in various ways. Combining multiple drugs is a trend in tumor treatment. <b>Methods:</b> In this article, we generated a novel tri‑specific antibody, called CiTE (CD3-BAFF-R-PD-L1), which is composed of a CD3 binding Fab frame, a BAFF-R binding scFv, and an additional scFv derived from PD‑L1. The cytotoxicity of T cells induced by CiTE (CD3-BAFF-R-PD-L1) was detected in combination with Chidamide. <b>Results:</b> The purified CiTE (CD3-BAFF-R-PD-L1) exhibited high binding capability for CD3-positive cells, BAFF-R-positive cells, and PD-L1-positive cells. Consequently, specific lysis towards BAFF-R-positive cell lines were induced by CiTE (CD3-BAFF-R-PD-L1) in the presence of T cells. We also confirmed that Chidamide could enhance T-cell mediated lysis by upregulating antigen strength on tumor cells and altering the TME by increasing the expression of T cell-attracting chemokines and costimulatory molecules. <b>Conclusions:</b> The novel tri-specific antibody combined with Chidamide holds promise as a safe and effective drug for the treatment of B-cell malignancies, due to its integration of three sections targeting different molecules into one compound.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 13","pages":"3907-3916"},"PeriodicalIF":3.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}