Cancer gene therapy最新文献_第3页

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

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

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

Blood-brain barrier alterations as an initiator of brain metastasis from lung cancer: a new take on an old story. 血脑屏障改变是肺癌脑转移的发起者：一个古老故事的新诠释。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-02 DOI: 10.1038/s41417-025-00916-6

Jianfen Wu, Haijian Wu, Fengqi Zhou, Yongjie Wang, Chun Wang, Jianxiong Ji

引用次数: 0

The activated tyrosine kinase ACK1 by multiple receptor tyrosine kinases promotes proliferation and invasion of mesothelioma via regulation of PI3K/AKT/mTOR and RAF/MAPK signaling pathways. 多受体酪氨酸激酶激活的酪氨酸激酶ACK1通过调控PI3K/AKT/mTOR和RAF/MAPK信号通路促进间皮瘤的增殖和侵袭。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-01 Epub Date: 2025-04-17 DOI: 10.1038/s41417-025-00904-w

Yue Qiao, Shuihao Zhu, Zhenni Liu, Natalia Kelley, Zhencang Zheng, Jonathan A Fletcher, Wen-Bin Ou

{"title":"The activated tyrosine kinase ACK1 by multiple receptor tyrosine kinases promotes proliferation and invasion of mesothelioma via regulation of PI3K/AKT/mTOR and RAF/MAPK signaling pathways.","authors":"Yue Qiao, Shuihao Zhu, Zhenni Liu, Natalia Kelley, Zhencang Zheng, Jonathan A Fletcher, Wen-Bin Ou","doi":"10.1038/s41417-025-00904-w","DOIUrl":"10.1038/s41417-025-00904-w","url":null,"abstract":"Activation of the receptor tyrosine kinases (RTKs) EGFR, MET, and AXL has been described in subsets of mesothelioma, suggesting that tyrosine kinases (TKs) might represent therapeutic targets in this chemotherapy resistant and highly lethal cancer. In the present study, activated TKs were identified in mesothelioma cells by phosphotyrosine immunoaffinity purification and tandem mass spectrometry, and biological functions were evaluated. The results showed that non-RTK activated-CDC42 kinase 1 (ACK1) was highly expressed and activated in 8 of 9 mesothelioma cell lines and 15 of 18 mesothelioma biopsies, but not in normal mesothelial cells. This ACK1 activation was in turn driven by the collective activation of EGFR, MET, and AXL. ACK1 inactivation by either a small molecule inhibitor (AIM-100) or RNAi had anti-proliferative, anti-migration, and pro-apoptotic effects in four mesothelioma cultures due to G1 arrest and xenograft model. These responses resulted from inhibition of the PI3K/AKT/mTOR and RAF/MAPK pathways, inhibition of cyclin A and cyclin D1, and up-regulation of cell cycle checkpoints TP53, CDKN1A (p21), and CDKN1B (p27). Combination treatment with AIM-100, cisplatin (CIS), and pemetrexed (PEM) had greater impact on mesothelioma response (apoptosis, proliferation arrest, and inhibition of migration and invasion) compared to administering only one or two of these agents. The current findings identify ACK1 as a single downstream target that can be inhibited to stymie these multiple receptor tyrosine kinase (EGFR, MET, and AXL) oncogenic programs in mesothelioma, and highlight that ACK1 inhibition, potentially in combination with PEM and CIS, warrants evaluation as a therapeutic strategy in mesothelioma.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":"678-689"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966944","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

Single-cell profiling of peripheral blood mononuclear cells from patients treated with oncolytic adenovirus TILT-123 reveals baseline immune status as a predictor of therapy outcomes. 接受溶瘤腺病毒TILT-123治疗的患者外周血单个核细胞的单细胞分析揭示了基线免疫状态作为治疗结果的预测因子。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2025-06-01 Epub Date: 2025-04-10 DOI: 10.1038/s41417-025-00901-z

Tatiana V Kudling, Dmitrii Bychkov, James H A Clubb, Santeri A Pakola, Victor Arias, Elise Jirovec, Mirte van der Heijden, Nea Ojala, Dafne C A Quixabeira, Lyna Haybout, Katriina J Jalkanen, Tuomo Alanko, Riikka Havunen, Suvi Sorsa, Claudia Kistler, Anna Kanerva, Otto Hemminki, Joao M Santos, Victor Cervera-Carrascon, Akseli Hemminki

{"title":"Single-cell profiling of peripheral blood mononuclear cells from patients treated with oncolytic adenovirus TILT-123 reveals baseline immune status as a predictor of therapy outcomes.","authors":"Tatiana V Kudling, Dmitrii Bychkov, James H A Clubb, Santeri A Pakola, Victor Arias, Elise Jirovec, Mirte van der Heijden, Nea Ojala, Dafne C A Quixabeira, Lyna Haybout, Katriina J Jalkanen, Tuomo Alanko, Riikka Havunen, Suvi Sorsa, Claudia Kistler, Anna Kanerva, Otto Hemminki, Joao M Santos, Victor Cervera-Carrascon, Akseli Hemminki","doi":"10.1038/s41417-025-00901-z","DOIUrl":"10.1038/s41417-025-00901-z","url":null,"abstract":"Oncolytic adenovirus Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (TILT-123, igrelimogene litadenorepvec) shows promise as a therapeutic agent capable of causing tumor regression and activating host immunity. A phase I clinical study TUNIMO (NCT04695327) assessed its safety as monotherapy in patients with various solid tumors. Through single-cell profiling of peripheral blood, we identified distinct immunological features distinguishing responders from non-responders. Specifically, at baseline, responders demonstrated enhanced cytotoxic markers and stronger immune cell communication networks. Moreover, higher baseline CD16+ monocytes correlated with improved survival, while elevated regulatory T cells predicted poor response. T and B cell evaluation revealed contrasting patterns: responders showed higher numbers of T cells with predicted specificity to both adenovirus and tumor antigens, while elevated total memory B cells, regardless of specificity, predicted poor survival. Several T and B cell receptor segments matched those previously reported in other viral infections, suggesting possible cross-reactive immune responses. These findings emphasize that comprehensive biomarker analysis of peripheral blood should include not only cell frequencies but also transcriptional changes and distinct patterns of cellular and humoral immunity.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":"649-661"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972771","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