Cancer gene therapy最新文献

Modified hTERT promoters-driven purine nucleoside phosphorylase-gene therapy in association with chemo- and targeted therapy in the context of ovarian cancer. 修饰hTERT启动子驱动的嘌呤核苷磷酸化酶基因治疗与卵巢癌化疗和靶向治疗相关

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-27 DOI: 10.1038/s41417-025-00932-6

Quoc Manh Nguyen, Pierre-François Dupré, Mathieu Berchel, Marylène Lévêque, Sylvie Choblet-Thery, Frédérique d'Arbonneau, Tristan Montier

{"title":"Modified hTERT promoters-driven purine nucleoside phosphorylase-gene therapy in association with chemo- and targeted therapy in the context of ovarian cancer.","authors":"Quoc Manh Nguyen, Pierre-François Dupré, Mathieu Berchel, Marylène Lévêque, Sylvie Choblet-Thery, Frédérique d'Arbonneau, Tristan Montier","doi":"10.1038/s41417-025-00932-6","DOIUrl":"https://doi.org/10.1038/s41417-025-00932-6","url":null,"abstract":"Ovarian cancer has the highest mortality-to-incidence ratio among gynecologic cancers worldwide. E.coli Purine Nucleoside Phosphorylase-based gene-directed enzyme prodrug therapy (PNP-GDEPT) offers a promising alternative for the treatment of solid tumors. This study proposes an original ovarian cancer treatment through the use of two recently developed modified hTERT promoters: the mutated hTERT (hTERTm) and the chimeric hTERT-CMV. Four plasmids were engineered to investigate the effects of cancer-specific PNP gene expression: pCMV-PNP, phTERT-PNP, phTERTm-PNP, and phTERT-CMV-PNP. The cationic lipid formulation BSV163/DOPE was employed to transfect PNP-coding plasmids into cisplatin-sensitive ovarian cancer cells and their resistant counterparts. hTERT-driven PNP-GDEPT selectively reduced cancer cell viability while sparing primary human fibroblasts. In addition, combining PNP-GDEPT with either cisplatin or olaparib further enhanced anticancer effects on cell viability and apoptosis. However, no combined effects were observed for the concurrent use of cisplatin and olaparib, with or without PNP-GDEPT. Our results demonstrate that targeted PNP-GDEPT has the potential to enhance the efficacy of chemotherapy and targeted therapy against ovarian cancer while minimizing side effects on healthy cells. This treatment is effective irrespective of cisplatin resistance status and warrants further investigation.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511604","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

Barriers and solutions for CAR-T therapy in solid tumors. CAR-T治疗实体肿瘤的障碍和解决方案。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-27 DOI: 10.1038/s41417-025-00931-7

Zhihao Tu, Yuelin Chen, Zhimi Zhang, Wanrong Meng, Ling Li

引用次数: 0

The dual role of GPX4 in breast cancer: mechanisms of therapeutic resistance and potential for novel targeted therapies. GPX4在乳腺癌中的双重作用：治疗耐药机制和新型靶向治疗的潜力。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-24 DOI: 10.1038/s41417-025-00927-3

Tingyu Gu, Kun Wang, Xiao Yuan, Haowen Tang, Shouchao Wang, Zhihong Zhao

{"title":"The dual role of GPX4 in breast cancer: mechanisms of therapeutic resistance and potential for novel targeted therapies.","authors":"Tingyu Gu, Kun Wang, Xiao Yuan, Haowen Tang, Shouchao Wang, Zhihong Zhao","doi":"10.1038/s41417-025-00927-3","DOIUrl":"https://doi.org/10.1038/s41417-025-00927-3","url":null,"abstract":"Glutathione peroxidase 4 (GPX4) is a key intracellular antioxidant enzyme that maintains oxidative homeostasis by catalyzing the reduction of lipid peroxides and relies on glutathione-specific inhibition of iron death. In recent years, it has been found that GPX4 exhibits significant aberrant expression in breast cancer (BC) and promotes BC development by regulating tumor cell proliferation, invasion, metastasis, and stem cell properties. More importantly, GPX4 overexpression leads to decreased sensitivity of BC to chemotherapy, radiotherapy, endocrine therapy, immune checkpoint inhibitors, and targeted therapies by inhibiting iron death, attenuating oxidative damage, and activating pro-survival signaling pathways. In this paper, we systematically review the molecular characterization of GPX4 and its cancer-promoting mechanism in BC, focusing on resolving its molecular regulatory network in multimodal therapy resistance. Based on the reversal of drug resistance and synergistic anti-tumor effects demonstrated by GPX4 inhibitors in preclinical studies, iron death induction strategies targeting GPX4 or combining with existing therapies are expected to be a new direction to overcome the bottleneck of drug resistance in BC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483226","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

UBE2N inhibition abrogates cancer chemoresistance and metastasis in lung adenocarcinoma. 抑制UBE2N可消除肺腺癌的化疗耐药和转移。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-22 DOI: 10.1038/s41417-025-00929-1

Zi-Mei Peng, Jin-Yong Xiong, Feng-Yi Deng, Xing Wang, Tao Wang, Chun-Xi Yang, Yan-Ru Chen, Xiao-Jian Han, Zhen Zhang

引用次数: 0

AAV for ovarian cancer gene therapy. AAV用于卵巢癌基因治疗。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-20 DOI: 10.1038/s41417-025-00926-4

Hee Chan Yoo, Sangkil Lee, Joong Yull Park, Eun-Ju Lee

{"title":"AAV for ovarian cancer gene therapy.","authors":"Hee Chan Yoo, Sangkil Lee, Joong Yull Park, Eun-Ju Lee","doi":"10.1038/s41417-025-00926-4","DOIUrl":"10.1038/s41417-025-00926-4","url":null,"abstract":"Recent advancements in ovarian cancer treatment, particularly with PARP inhibitors, have markedly enhanced the recurrence-free interval, shifting the treatment paradigm and increasing treatment success in patients with BRCA mutations or HRD (homologous recombination deficiency). However, a significant proportion of cases experience relapse, resulting in poorer long-term survival rates when compared to other female cancers, such as breast cancer. This review explores the potential of adeno-associated virus (AAV) vectors for gene therapy in ovarian cancer and examines rational gene therapy strategies by categorizing them based on target cells and target genes to determine the most effective approach for ovarian cancer treatment. Specifically, it examines strategies such as anti-angiogenesis and immune modulation, highlighting the strategy of gene supplementation to hinder ovarian cancer progression. Innovations in AAV capsid design now allow for targeted delivery, focusing on ovarian cancer stem cells (CSCs) identified by specific markers. Additionally, leveraging DNA sequencing technologies enhances the identification and incorporation of therapeutic genes into AAV vectors, promising new avenues for ovarian cancer gene therapy.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336321","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

Blocking the functional domain of cancer cell surface TIP1 upregulates Midkine via the β-catenin/Wnt signaling pathway. 阻断癌细胞表面TIP1的功能域可通过β-catenin/Wnt信号通路上调Midkine。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-18 DOI: 10.1038/s41417-025-00922-8

Minakshi Saikia, Harendra Kumar Shah, Dennis E Hallahan, Abhay Kumar Singh, Vaishali Kapoor

{"title":"Blocking the functional domain of cancer cell surface TIP1 upregulates Midkine via the β-catenin/Wnt signaling pathway.","authors":"Minakshi Saikia, Harendra Kumar Shah, Dennis E Hallahan, Abhay Kumar Singh, Vaishali Kapoor","doi":"10.1038/s41417-025-00922-8","DOIUrl":"https://doi.org/10.1038/s41417-025-00922-8","url":null,"abstract":"Drug resistance exhibited by cancer cells remains one of the primary reasons for the failure of therapeutic approaches to increase the survival of cancer patients. Marginal improvement in therapeutic efficacy with current treatment approaches for non-small cell lung cancer (NSCLC) mandates new treatment strategies. Tax interacting Protein-1 (TIP1) is a radiation-inducible molecular target involved in various cancer pathways. TIP1 expression correlates with poor survival in NSCLC patients. Antibody blocking the functional domain of TIP1 reduced cell proliferation and sensitized cancer cells to radiation. A ten-fold increase in Midkine (MDK) was observed in the proteomic analysis of cells treated with anti-TIP1 antibody. Wnt signaling activation led to MDK upregulation at the mRNA and protein levels following TIP1 blockade. Genetic silencing of β-catenin abrogated the induction of MDK following anti-TIP1 antibody treatment. Inhibiting TIP1 along with MDK showed a reduction in the colony-forming capability of the cells, indicating that MDK upregulation might be a strategy employed by cancer cells to combat the anti-proliferative capabilities of the anti-TIP1 antibody. Co-targeting cell surface TIP1 and MDK may be an effective therapeutic strategy for NSCLC patients.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324592","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

Identification of an immunomodulatory lncRNA signature associated with immune cell reprogramming in high-grade glioma. 鉴定高级别胶质瘤中与免疫细胞重编程相关的免疫调节lncRNA特征。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-17 DOI: 10.1038/s41417-025-00919-3

Alessandro Canella, Prajwal Rajappa

{"title":"Identification of an immunomodulatory lncRNA signature associated with immune cell reprogramming in high-grade glioma.","authors":"Alessandro Canella, Prajwal Rajappa","doi":"10.1038/s41417-025-00919-3","DOIUrl":"https://doi.org/10.1038/s41417-025-00919-3","url":null,"abstract":"High-grade gliomas (HGGs) are among the most aggressive brain tumors in pediatric, adolescent, and young adult (AYA) cancer patients, with a median survival of 12-15 months post-diagnosis. Their poor prognosis is driven by a highly immunosuppressive tumor immune microenvironment (TIME), which inhibits cytotoxic immune infiltration and anti-tumor response. This study investigated the involvement of long non-coding RNAs (lncRNAs) in shaping the immune phenotype of HGGs using two murine models: RCAS-PDGFb representing an immunosuppressive TME, and RCAS-BRAF V600E characterized by a signature more consistent with a pro-inflammatory TME. Transcriptomic analysis of tumor-infiltrating immune cells identified distinct lncRNA signatures associated with immunosuppressive and pro-inflammatory TMEs. Single-cell RNA sequencing and spatial transcriptomics supported context-dependent expression of these lncRNAs in high-grade glioma-associated immune cells, such as myeloid, T, and NK cells, and revealed their spatial distribution within the glioblastoma (GBM) TME. Several lncRNAs were enriched at the tumor edge and within necrotic regions in GBM patient samples, correlating with immunosuppression reprogramming and immune evasion mechanisms. These findings highlight specific immunomodulatory lncRNAs as potential players in the immunosuppressive glioma TME, and likely candidates for future studies aimed at developing novel therapeutic strategies to overcome immune suppression and improve clinical outcomes.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315929","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

Retraction Note: HADHA promotes glioma progression by accelerating MDM2-mediated p53 ubiquitination. 备注：HADHA通过加速mdm2介导的p53泛素化来促进胶质瘤的进展。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-17 DOI: 10.1038/s41417-025-00924-6

Rudong Chen, Hao Chen, Changchen Hu

引用次数: 0

Oleuropein regulates ubiquitination-mediated Mcl-1 turnover and exhibits antitumor activity. 橄榄苦苷调节泛素化介导的Mcl-1周转并显示抗肿瘤活性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-12 DOI: 10.1038/s41417-025-00921-9

Wen Liu, Song Peng, Jinzhuang Liao, Ruirui Wang, Pengfei Guo, Wei Li

{"title":"Oleuropein regulates ubiquitination-mediated Mcl-1 turnover and exhibits antitumor activity.","authors":"Wen Liu, Song Peng, Jinzhuang Liao, Ruirui Wang, Pengfei Guo, Wei Li","doi":"10.1038/s41417-025-00921-9","DOIUrl":"https://doi.org/10.1038/s41417-025-00921-9","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) represents the most common type of malignant oral tumor, with a high prevalence globally. Despite continual advancements in OSCC treatment, the 5-year survival rate remains around 50%, highlighting an urgent need for the development of new and effective therapeutic strategies. Here, we focused on myeloid leukemia 1 (Mcl-1), a well-known oncogenic driver in various human cancers, and systematically explored the therapeutic potential of oleuropein (Ole) through in vitro and in vivo analyses. Our findings demonstrated that Ole suppressed OSCC cell viability dose-dependently. Mechanistically, Ole facilitated β-TRCP-mediated ubiquitination of Mcl-1 by inhibiting the Akt-GSK3β-Mcl-1 pathway and enhancing the collaboration between β-TRCP and Mcl-1, ultimately leading to Mcl-1 degradation. Furthermore, the knockdown of β-TRCP mitigated the inhibitory effects of Ole on OSCC cells. In agreement with our cell-based experiments, animal studies showed that Ole treatment significantly delayed tumor growth without causing toxicity to vital organs. Additionally, whether used alone or combined with radiation, Ole effectively overcame radioresistance in OSCC cells. Our results suggest that Ole is a promising anti-tumor agent capable of treating OSCC by targeting Mcl-1.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282453","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

Ending nuclear weapons, before they end us. 在核武器终结我们之前终结它们。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-10 DOI: 10.1038/s41417-025-00920-w

Kamran Abbasi, Parveen Ali, Virginia Barbour, Marion Birch, Inga Blum, Peter Doherty, Andy Haines, Ira Helfand, Richard Horton, Kati Juva, Jose F Lapena, Robert Mash, Olga Mironova, Arun Mitra, Carlos Monteiro, Elena N Naumova, David Onazi, Tilman Ruff, Peush Sahni, James Tumwine, Carlos Umaña, Paul Yonga, Chris Zielinski

引用次数: 0