Cancer gene therapy最新文献_第7页

Emerging roles of prohibitins in cancer: an update 禁止药物在癌症中的新作用：最新进展。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-03-08 DOI: 10.1038/s41417-025-00883-y

Yunliang Gao, Yuanyuan Tang

引用次数: 0

Chimeric Ad5/35 oncolytic adenovirus overcome preexisting neutralizing antibodies and enhance tumor targeting efficiency 嵌合Ad5/35溶瘤腺病毒克服了先前存在的中和抗体，提高了肿瘤靶向效率。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-03-08 DOI: 10.1038/s41417-025-00884-x

Zhoutong Dai, Yao Si, Shengfeng Xiong, Ying Li, Jiaqi Ye, Qinglei Gao, Ding Ma, Xin Jin, Fei Li

{"title":"Chimeric Ad5/35 oncolytic adenovirus overcome preexisting neutralizing antibodies and enhance tumor targeting efficiency","authors":"Zhoutong Dai, Yao Si, Shengfeng Xiong, Ying Li, Jiaqi Ye, Qinglei Gao, Ding Ma, Xin Jin, Fei Li","doi":"10.1038/s41417-025-00884-x","DOIUrl":"10.1038/s41417-025-00884-x","url":null,"abstract":"KD01, a third-generation conditionally replicating adenovirus serotype 5 developed by our team, has approved by the China Center for Drug Evaluation (CDE) for Phase I clinical trials (NCT06552598). However, 60% seroprevalence of anti-Ad5 neutralizing antibodies is a major hurdle for Ad5-based oncolytic viruses. To address this issue, we developed oAd5/35-HF, a fourth-generation oncolytic adenovirus vector designed to enhance infection efficiency and evade pre-existing neutralizing antibodies (NABs). To achieve this, we introduced targeted capsid modifications, replacing hexon hypervariable regions (HVRs) 1 and 5 with those from adenovirus serotype 35 (Ad35), along with alterations to the fiber region. These combined modifications significantly improved infection efficiency, maintained high viral titers, and enabled the virus to resist NABs. This is the first report of replacing both the Ad5 hexon HVRs and fiber regions with those from Ad35 in an oncolytic adenovirus, resulting in potent antitumor activity across multiple cancer types, even in the presence of high NAB levels. The oAd5/35-HF backbone provides a versatile platform for developing new chimera oncolytic adenovirus and adenovirus vector-based vaccine.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 4","pages":"418-436"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ferroptosis enhances the therapeutic potential of oncolytic adenoviruses KD01 against cancer 铁下垂增强溶瘤腺病毒KD01对癌症的治疗潜力。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-03-03 DOI: 10.1038/s41417-025-00882-z

Wenhuan Li, Teng Ji, Jiaqi Ye, Shengfeng Xiong, Yao Si, Xiaohui Sun, Fei Li, Zhoutong Dai

{"title":"Ferroptosis enhances the therapeutic potential of oncolytic adenoviruses KD01 against cancer","authors":"Wenhuan Li, Teng Ji, Jiaqi Ye, Shengfeng Xiong, Yao Si, Xiaohui Sun, Fei Li, Zhoutong Dai","doi":"10.1038/s41417-025-00882-z","DOIUrl":"10.1038/s41417-025-00882-z","url":null,"abstract":"Oncolytic virotherapy has emerged as a promising strategy for cancer treatment by selectively targeting and lysing tumor cells. However, its efficacy is often limited in certain tumor types due to multiple factors. This study explores the combination of oncolytic adenoviruses with Erastin, a potent ferroptosis inducer, to enhance antitumor efficacy in oncolytic virus-insensitive cancer cell lines. In vitro experiments demonstrated that Erastin significantly increased the cytotoxicity of oncolytic virotherapy, leading to greater inhibition of cell proliferation and elevated rates of cell death compared to monotherapies. The combination treatment further promoted ferroptosis, as evidenced by increased reactive oxygen species (ROS) levels, enhanced lipid peroxidation, and disrupted redox homeostasis. RNA sequencing identified the downregulation of Dickkopf-1 (DKK1) as a key mediator of the enhanced ferroptotic effect. Restoring the expression of DKK1 partially mitigated the cytotoxic effects of the combination therapy, highlighting its crucial role in mediating the enhanced ferroptosis-induced oncolytic virotherapy efficacy. In vivo studies further validated these findings, demonstrating that the combined treatment significantly reduced tumor growth without inducing notable toxicity. This novel therapeutic approach has great potential to enhance the efficacy of oncolytic virotherapy in cancers resistant to oncolytic viruses by inducing ferroptosis. Further investigation in clinically relevant models is warranted to fully elucidate the underlying mechanisms and to optimize this combination strategy for potential clinical applications.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 4","pages":"403-417"},"PeriodicalIF":4.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-025-00882-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540160","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}

引用次数: 0

Therapeutic targeting of the tryptophan-kynurenine-aryl hydrocarbon receptor pathway with apigenin in MED12-mutant leiomyoma cells 芹菜素靶向治疗med12突变型平滑肌瘤细胞中的色氨酸-犬尿氨酸-芳烃受体通路。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-03-01 DOI: 10.1038/s41417-025-00881-0

Takashi Iizuka, Azna Zuberi, Helen Wei, John S. Coon V, Melania Lidia Anton, Kadir Buyukcelebi, Mazhar Adli, Serdar E. Bulun, Ping Yin

{"title":"Therapeutic targeting of the tryptophan-kynurenine-aryl hydrocarbon receptor pathway with apigenin in MED12-mutant leiomyoma cells","authors":"Takashi Iizuka, Azna Zuberi, Helen Wei, John S. Coon V, Melania Lidia Anton, Kadir Buyukcelebi, Mazhar Adli, Serdar E. Bulun, Ping Yin","doi":"10.1038/s41417-025-00881-0","DOIUrl":"10.1038/s41417-025-00881-0","url":null,"abstract":"Approximately 77.4% of uterine leiomyomas carry MED12 gene mutations (mut-MED12), which are specifically associated with strikingly upregulated expression and activity of the tryptophan 2,3-dioxygenase (TDO2) enzyme, leading to increased conversion of tryptophan to kynureine. Kynurenine increases leiomyoma cell survival by activating the aryl hydrocarbon receptor (AHR). We used a leiomyoma-relevant model, in which a MED12 Gly44 mutation was knocked in by CRISPR in a human uterine myometrial smooth muscle (UtSM) cell line, in addition to primary leiomyoma cells from 26 patients to ascertain the mechanisms responsible for therapeutic effects of apigenin, a natural compound. Apigenin treatment significantly decreased cell viability, inhibited cell cycle progression, and induced apoptosis preferentially in mut-MED12 versus wild-type primary leiomyoma and UtSM cells. Apigenin not only blocked AHR action but also decreased TDO2 expression and kynurenine production, preferentially in mut-MED12 cells. Apigenin did not alter TDO2 enzyme activity. TNF and IL-1β, cytokines upregulated in leiomyoma, strikingly induced TDO2 expression levels via activating the NF-κB and JNK pathways, which were abolished by apigenin. Apigenin or a TDO2 inhibitor decreased UtSM cell viability induced by TNF/IL-1β. We provide proof-of-principle evidence that apigenin is a potential therapeutic agent for mut-MED12 leiomyomas.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 4","pages":"393-402"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A conditionally replicative adenovirus vector containing the synNotch receptor gene for the treatment of muscle-invasive bladder cancer 含synNotch受体基因的条件复制腺病毒载体治疗肌肉侵袭性膀胱癌。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-02-26 DOI: 10.1038/s41417-025-00879-8

Ruhan A, Hideto Ueki, Shunya Nishioka, Rion Yamazaki, Marina Maekawa, Koichi Kitagawa, Hideaki Miyake, Toshiro Shirakawa

{"title":"A conditionally replicative adenovirus vector containing the synNotch receptor gene for the treatment of muscle-invasive bladder cancer","authors":"Ruhan A, Hideto Ueki, Shunya Nishioka, Rion Yamazaki, Marina Maekawa, Koichi Kitagawa, Hideaki Miyake, Toshiro Shirakawa","doi":"10.1038/s41417-025-00879-8","DOIUrl":"10.1038/s41417-025-00879-8","url":null,"abstract":"Muscle-invasive bladder cancer (MIBC), a highly heterogeneous disease, shows genomic instability and a high mutation rate, making it difficult to treat. Recent studies revealed that cancer stem cells (CSCs) play a critical role in MIBC frequent recurrence and high morbidity. Previous research has shown that Cyclooxygenases-2 (COX-2) is particularly highly expressed in bladder cancer cells. In recent years, the development of oncolytic adenoviruses and their use in clinical trials have gained increased attention. In this study, we composed a conditionally replicative adenovirus vector (CRAd-synNotch) that carries the COX-2 promotor driving adenoviral E1 gene, the synNotch receptor therapeutic gene, and the Ad5/35 fiber gene. Activation of the COX-2 promoter gene causes replication only within COX-2 expressing cancer cells, thereby leading to tumor oncolysis. Also, CD44 and HIF signals contribute to cancer stemness and maintaining CSCs in bladder cancer, and the transduced synNotch receptor inhibits both CD44 and HIF signals simultaneously. We performed an in vivo study using a mouse xenograft model of T24 human MIBC cells and confirmed the significant antitumor activity of CRAd-synNotch. Our findings in this study warrant the further development of CRAd-synNotch for treating patients with MIBC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 3","pages":"306-317"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-025-00879-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514788","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}

引用次数: 0

The role of tumor-derived exosomal LncRNA in tumor metastasis 肿瘤源性外泌体LncRNA在肿瘤转移中的作用。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-02-26 DOI: 10.1038/s41417-024-00852-x

Zhile Yu, Jiali Fu, Vanya Mantareva, Ivica Blažević, Yusong Wu, Dianchang Wen, Tungalag Battulga, Yuqing Wang, Jianye Zhang

引用次数: 0

FXYD5 regulates gastric cancer cell metastasis and drug resistance by EMT modulation FXYD5通过EMT调控胃癌细胞转移和耐药。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-02-21 DOI: 10.1038/s41417-025-00878-9

Yuning Mao, Yaohua Hu, Han Meng, Jing Qin, Qingling An, Caiqin Zhang, Chenbo Guo, Yong Zhao, Dengxu Tan, Xu Ge, Changhong Shi

{"title":"FXYD5 regulates gastric cancer cell metastasis and drug resistance by EMT modulation","authors":"Yuning Mao, Yaohua Hu, Han Meng, Jing Qin, Qingling An, Caiqin Zhang, Chenbo Guo, Yong Zhao, Dengxu Tan, Xu Ge, Changhong Shi","doi":"10.1038/s41417-025-00878-9","DOIUrl":"10.1038/s41417-025-00878-9","url":null,"abstract":"Gastric cancer (GC) is the third leading cause of cancer-related mortality and the fourth most prevalent malignancy globally. The high prevalence and mortality rates of GC are attributed to various factors, including drug resistance, local recurrence, and distant metastases. There is an urgent need to identify novel therapeutic targets for GC. Patient-derived xenografts (PDX) model offers unique advantages in maintaining the molecular heterogeneity and tumor microenvironment of primary tumors, offering significant advantages for the screening of personalized therapeutic targets. In this study, we established GC PDX models with metastatic potential through orthotopic transplantation and investigated the different gene expressions between primary and metastatic tumors using PCR-array analysis. We found that the metastatic tumors displayed elevated levels of FXYD domain-containing ion transport regulator 5 (FXYD5) compared to the primary tumors. Additionally, reducing FXYD5 expression was found to inhibit the invasion, metastasis, and proliferation of GC cells. Silencing FXYD5 also reversed the resistance of GC cells to doxorubicin and vincristine by modulating the epithelial–mesenchymal transition (EMT) process and the expression of multidrug resistance protein 2. This study indicates that FXYD5 is involved in GC progression and regulates chemotherapy resistance, suggesting its potential as a novel therapeutic target for the clinical treatment of GC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 3","pages":"318-326"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SMARCB1-driven EGFR-GLI1 epigenetic alterations in lung cancer progression and therapy are differentially modulated by MEOX2 and GLI-1 smarcb1驱动的EGFR-GLI1表观遗传改变在肺癌进展和治疗中受到MEOX2和gli1的差异调节。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-02-19 DOI: 10.1038/s41417-025-00873-0

Octavio A. Trejo-Villegas, Priscila Pineda-Villegas, Leonel Armas-López, Criselda Mendoza-Milla, Irlanda Peralta-Arrieta, Oscar Arrieta, Irene H. Heijink, Joaquín Zúñiga, Federico Ávila-Moreno

{"title":"SMARCB1-driven EGFR-GLI1 epigenetic alterations in lung cancer progression and therapy are differentially modulated by MEOX2 and GLI-1","authors":"Octavio A. Trejo-Villegas, Priscila Pineda-Villegas, Leonel Armas-López, Criselda Mendoza-Milla, Irlanda Peralta-Arrieta, Oscar Arrieta, Irene H. Heijink, Joaquín Zúñiga, Federico Ávila-Moreno","doi":"10.1038/s41417-025-00873-0","DOIUrl":"10.1038/s41417-025-00873-0","url":null,"abstract":"Lung cancer remains the leading cause of cancer-related mortality globally, with genes such as SMARCB1, MEOX2, and GLI-1 playing significant roles in its malignancy. Despite their known involvement, the specific molecular contributions of these genes to lung cancer progression, particularly their effects on epigenetic modifications on oncogenes sequences as EGFR and GLI-1, and their influence in the response to EGFR-TKI-based therapies, have not been fully explored. Our study reveals how MEOX2 and GLI-1 are key molecular modulators of the GLI-1 and EGFR-epigenetic patterns, which in turn transcriptionally and epigenetically affect EGFR gene expression in lung cancer. Additionally, MEOX2 was found to significantly promote in vivo lung tumor progression and diminish the effectiveness of EGFR-TKI therapies. Conversely, mSWI/SNF derived subunit SMARCB1 was detected to suppress tumor growth and enhance the oncological therapeutic response in in vivo studies by inducing epigenetic modifications in the GLI-1 and EGFR genetic sequences. Furthermore, our results suggest that BRD9 may contribute to the activation of both lung cancer oncogenes GLI-1 and EGFR. Such findings suggest that SMARCB1 and MEOX2 could serve as important prognosis biomarkers and target genes in human lung cancer therapy, offering new opportunities for the development of more effective and selective treatment strategies in the field of lung malignant diseases.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 3","pages":"327-342"},"PeriodicalIF":4.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-025-00873-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456951","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}

引用次数: 0

Editorial Expression of Concern: p73β-expressing recombinant adenovirus: a potential anticancer agent 编辑关注表达：表达p73β的重组腺病毒：一种潜在的抗癌药物。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-02-13 DOI: 10.1038/s41417-025-00877-w

Sanjeev Das, Srikanth Nama, Sini Antony, Kumaravel Somasundaram

引用次数: 0

Biodistribution and toxicity evaluation of oncolytic adenovirus Adf35(OGN) in Syrian hamster and mouse 溶瘤腺病毒Adf35（OGN）在叙利亚仓鼠和小鼠体内的生物分布和毒性评价。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-02-11 DOI: 10.1038/s41417-025-00875-y

Erik Yngve, Malin Eriksson, Anders Hedin, Arwa Ali, Chuan Jin, Olle Korsgren, Di Yu

{"title":"Biodistribution and toxicity evaluation of oncolytic adenovirus Adf35(OGN) in Syrian hamster and mouse","authors":"Erik Yngve, Malin Eriksson, Anders Hedin, Arwa Ali, Chuan Jin, Olle Korsgren, Di Yu","doi":"10.1038/s41417-025-00875-y","DOIUrl":"10.1038/s41417-025-00875-y","url":null,"abstract":"Oncolytic adenovirus has been widely evaluated as a cancer treatment agent with tolerable toxicity profile. We have recently developed a new oncolytic adenovirus Adf35(OGN) with two immunostimulatory transgenes alpha-1,3-galactosyltransferase (GGTA1) from Sus scrofa and neutrophil-activating protein (NAP) from Helicobacter pylori. Adf35(OGN) can kill tumor cells and trigger a strong immune response against tumor antigens. Here, we report the toxicity and biodistribution of Adf35(OGN) in Syrian hamster and GGTA1-knockout mouse. The virus was delivered subcutaneously in naïve hamsters and intratumorally in GGTA1-knockout mouse in multiple doses at dosages of 1–5 × 1011 viral particles (VP)/kg. The virus did not replicate in any tissues, evidenced as low or no viral copies detected by qPCR. The virus was also found at low levels in biofluids (saliva, urine, and feces), indicating that spread to the environment is low with a low risk of secondary infections via shedding. The virus did not cause any biochemical, hematological, or histopathological alterations. In summary, Adf35(OGN) has a good safety profile in these animal models and these results support future clinical evaluation for Adf35(OGN).","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 3","pages":"297-305"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-025-00875-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398237","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}

引用次数: 0