Cancer gene therapy最新文献

{"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":"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":"32 7","pages":"793-805"},"PeriodicalIF":5.0,"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}

{"title":"Ending nuclear weapons, before they end us","authors":"Kamran Abbasi, Parveen Ali, Virginia Barbour, Marion Birch, Inga Blum, Peter Doherty, Andy Haines, Ira Helfand, Richard Horton, Kati Juva, Jose F. Lapena Jr, 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","doi":"10.1038/s41417-025-00920-w","DOIUrl":"10.1038/s41417-025-00920-w","url":null,"abstract":"","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 8","pages":"807-808"},"PeriodicalIF":5.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41417-025-00920-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265316","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":"Blood-brain barrier alterations as an initiator of brain metastasis from lung cancer: a new take on an old story","authors":"Jianfen Wu, Haijian Wu, Fengqi Zhou, Yongjie Wang, Chun Wang, Jianxiong Ji","doi":"10.1038/s41417-025-00916-6","DOIUrl":"10.1038/s41417-025-00916-6","url":null,"abstract":"Lung cancer is the most common primary tumor associated with brain metastases. Currently, the molecular mechanisms underlying the pathogenesis of lung cancer brain metastasis (LCBM) have not been fully elucidated and effective therapeutic strategies for treating this disease are still lacking. The blood-brain barrier (BBB) is a selectively permeable membrane and is crucial in maintaining brain homeostasis. Increasing evidence from clinical and pre-clinical studies indicated that metastatic circulating tumor cells from lung cancer can affect the cellular biology of BBB components, and destruct its integrity as well as function to penetrate the BBB to clone in the brain parenchyma, therein producing malignant secondary tumors. Therefore, in this review, we aim to discuss about the involvement of BBB alterations during the initiation of LCBM and the cellular and molecular mechanisms underlying. A better understanding of these pathophysiological processes may help open avenues to develop new therapeutic strategies to prevent or treat this notorious disease.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 8","pages":"809-816"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207755","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}

{"title":"Platelet activation: a barrier to effective antitumor immunity","authors":"Daolin Tang, Rui Kang","doi":"10.1038/s41417-025-00915-7","DOIUrl":"10.1038/s41417-025-00915-7","url":null,"abstract":"Platelets, traditionally known for their role in hemostasis, are now recognized as key modulators of oncological processes, influencing tumor growth and metastasis through interactions with the tumor microenvironment. Recent studies reveal that platelet activation contributes to T-cell exhaustion by releasing thromboxane A2 (TXA2), which binds to the TBXA2R receptor and activates ARHGEF1, a guanine nucleotide exchange factor (GEF), leading to the suppression of T-cell function. This editorial explores the potential of repurposing anti-platelet drugs, such as aspirin, to counteract these effects. Aspirin, by inhibiting cyclooxygenase enzymes essential for TXA2 synthesis, can enhance T-cell activity in metastatic contexts, thereby improving immune surveillance and response. We advocate for further investigation into the thromboxane pathway’s impact on T-cell functionality and the development of aspirin-based therapeutic strategies to combat cancer metastasis.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 7","pages":"741-743"},"PeriodicalIF":5.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41417-025-00915-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157047","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":"Hemorrhagic and ischemic risks of anti-VEGF therapies in glioblastoma","authors":"Ozal Beylerli, Ilgiz Gareev, Andrey Kaprin, Aamir Ahmad, Vladimir Chekhonin, Shanshan Yang, Guang Yang","doi":"10.1038/s41417-025-00914-8","DOIUrl":"10.1038/s41417-025-00914-8","url":null,"abstract":"Glioblastoma (GBM) is one of the most aggressive primary brain tumors, characterized by extensive neovascularization and a highly infiltrative phenotype. Anti-vascular endothelial growth factor (VEGF) therapies, such as bevacizumab, have emerged as significant adjunct treatments for recurrent and high-grade GBM by targeting abnormal tumor vasculature. Despite demonstrated benefits in slowing tumor progression and alleviating peritumoral edema, these agents are associated with notable vascular complications, including hemorrhagic and ischemic events. Hemorrhagic complications range from minor intracranial microbleeds to life-threatening intracranial hemorrhages (ICH). Mechanistically, VEGF inhibition disrupts endothelial function and decreases vascular integrity, making already fragile tumor vessels prone to rupture. Glioma-associated vascular abnormalities, including disorganized vessel networks and compromised blood-brain barrier, further exacerbate bleeding risks. Concurrent use of anticoagulants, hypertension, and genetic predispositions also significantly elevate hemorrhagic risk. In addition to bleeding complications, ischemic events are increasingly recognized in patients receiving anti-VEGF therapy. Reduced vascular endothelial cells (ECs) survival and diminished microvascular density can lead to regional hypoperfusion and potentially precipitate cerebrovascular ischemia. Impaired vasoreactivity and increased vascular resistance, often accompanied by endothelial dysfunction and microvascular rarefaction, contribute to elevated stroke and arterial thrombotic risk. This review synthesizes current evidence on hemorrhagic and ischemic complications arising from anti-VEGF therapy in GBM. We discuss underlying pathophysiological mechanisms, risk factors, and clinically relevant biomarkers, as well as prevention strategies—such as rigorous blood pressure (BP) control and close monitoring of coagulation parameters. We further highlight emerging avenues in precision medicine, including pharmacogenomic profiling and targeted adjunct agents that protect vascular integrity, aimed at mitigating adverse vascular events while preserving therapeutic efficacy. The goal is to optimize outcomes for GBM patients by balancing the benefits of anti-VEGF therapy with vigilant management of its inherent vascular risks. In addition, this study analyzes existing clinical trials of the use of anti-VEGF drugs in the treatment of gliomas using data from the clinicaltirals.gov website.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 7","pages":"762-777"},"PeriodicalIF":5.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109967","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}

{"title":"Pan-cancer oncogenic properties and therapeutic potential of SF3B4","authors":"Yanmei Shi, Qimei Pan, Wenli Chen, Limin Xie, Shiru Tang, Zhizhi Yang, Man Zhang, Dong Yin, Lehang Lin, Jian-You Liao","doi":"10.1038/s41417-025-00910-y","DOIUrl":"10.1038/s41417-025-00910-y","url":null,"abstract":"Splicing factor 3B (SF3B) subunit 4 (SF3B4), an SF3B complex component essential for spliceosome assembly and accurate splicing, plays a major role in cancer development. However, the precise mechanism through which SF3B4 contributes to tumor growth remains unclear. Here, we demonstrate that SF3B4 is strongly expressed in patients with various cancer types and correlated with their survival. By using hepatocellular carcinoma (HCC) as a model, we reveal that SF3B4’s interactions with and regulatory influence on the checkpoint protein BUB1 are essential for appropriate cancer cell mitosis and proliferation. Our results thus demonstrate the roles of SF3B4 as both a cell-cycle regulator and an oncogenic factor in HCC, highlighting its potential as a pan-cancer therapeutic target and diagnostic biomarker.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 6","pages":"706-720"},"PeriodicalIF":5.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109970","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}

{"title":"Human endogenous retroviruses (HERVs) associated with glioblastoma risk and prognosis","authors":"Harun Mazumder, Hui-Yi Lin, Melody Baddoo, Wojciech Gałan, Diana Polania-Villanueva, Chindo Hicks, David Otohinoyi, Francesca Peruzzi, Zbigniew Madeja, Victoria P. Belancio, Erik K. Flemington, Krzysztof Reiss, Monika Rak","doi":"10.1038/s41417-024-00868-3","DOIUrl":"10.1038/s41417-024-00868-3","url":null,"abstract":"Emerging evidence suggests expression from human endogenous retrovirus (HERV) loci likely contributes to, or is a biomarker of, glioblastoma multiforme (GBM) disease progression. However, the relationship between HERV expression and GBM malignant phenotype is unclear. Applying several in silico analyses based on data from The Cancer Genome Atlas (TCGA), we derived a locus-specific HERV transcriptome for glioma that revealed 211 HERVs significantly dysregulated in the comparisons of GBM vs. normal brain (NB), GBM vs. low-grade glioma (LGG), and LGG vs. NB. Our analysis supported development of a unique HERV scoring algorithm that segregated GBM, LGG, and NB. Interestingly, lower HERV scores showed correlation with lower survival in GBM. However, HERV scores were less robust in predicting LGG survival or LGG progression to GBM. Functional prediction analysis linked the 211 HERV loci with 18 voltage-gated potassium channel genes. The functional link between dysregulated HERVs and specific potassium channel genes may contribute to better understanding of GBM pathogenesis, disease progression, and possibly drug resistance.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 6","pages":"622-632"},"PeriodicalIF":5.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101467","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":"Structural regulation of PLK1 activity: implications for cell cycle function and drug discovery","authors":"Danda Chapagai, Klaus Strebhardt, Michael D. Wyatt, Campbell McInnes","doi":"10.1038/s41417-025-00907-7","DOIUrl":"10.1038/s41417-025-00907-7","url":null,"abstract":"Polo Like Kinase 1 (PLK1), a key regulator of mitosis whose overexpression is often associated with poor survival rates in cancer, continues to be widely investigated as an oncology drug target with clinical trials evaluating second and third generation inhibitors. In addition to the conserved N-terminal kinase domain (KD), a unique characteristic of the Polo-Like kinase family is the C-terminal polo-box domain (PBD). The PBD contains a phosphopeptide binding site that recognizes substrates primed by other kinases and furthermore is responsible for subcellular localization of PLK1 to specific sites in the nucleus including centrosomes and kinetochores. Another role of the PBD is its regulatory ability through domain-domain interactions with the KD to maintain an autoinhibited state of PLK1. Insights into post translational modifications and the PBD – KD domain-domain association have been obtained and show that key events in PLK1 regulation include phosphosubstrate binding, T210 phosphorylation and engagement with the Bora protein. These can induce an open and active conformation where the domain-domain inhibitory interactions no longer dominate. Further regulatory events recently described include the interchange between monomeric and dimeric forms, which can also serve to inhibit or activate PLK1 during the cell cycle. Different oligomeric forms of PLK1, existing as homodimers and heterodimers with PLK2, have been identified and likely play context dependent roles. This review provides an overview of recent information describing structural and mechanistic insights into inhibition of PLK1 and the temporal and spatial requirements of its activation and regulation. It also covers recent insights into the conformational regulation of other members of the Polo-Like kinase family. The implications of the conformational regulation of PLK1 with respect to cell cycle function and drug discovery are significant and are therefore discussed in detail.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 6","pages":"608-621"},"PeriodicalIF":5.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086118","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":"Old versus new: upstream and downstream of promyelocytic leukemia zinc finger protein","authors":"Kai Wang, Deyu Guo, Shijie Sun, Kang Tian, Hongchang Shen, Jiajun Du","doi":"10.1038/s41417-025-00912-w","DOIUrl":"10.1038/s41417-025-00912-w","url":null,"abstract":"Promyelocytic leukemia zinc finger (PLZF) is a member of the zinc finger protein family and has been extensively studied due to its crucial role in influencing stem cell self-renewal, spermatogenesis, T cell differentiation, tumorigenesis, and development. Its function is regulated by multidimensional and multilevel regulation. Recent studies have explored the mechanism of action of PLZF in different diseases and related treatment strategies. This study aimed to summarize the regulatory mechanisms underlying PLZF expression and function, and update the latest PLZF regulatory targets and interacting molecules. We also summarized the mechanism by which PLZF promoted the transcriptional activation of target genes, besides its role as a transcriptional repressor. This study revealed a more detailed upstream and downstream regulatory mechanism of PLZF, providing directions for future research.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 7","pages":"750-761"},"PeriodicalIF":5.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973920","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}

{"title":"Retraction Note: Nrf2 overexpression increases the resistance of acute myeloid leukemia to cytarabine by inhibiting replication factor C4","authors":"Tianzhen Hu, Chengyun Pan, Tianzhuo Zhang, Ming Ni, Weili Wang, Siyu Zhang, Ying Chen, Jishi Wang, Qin Fang","doi":"10.1038/s41417-025-00913-9","DOIUrl":"10.1038/s41417-025-00913-9","url":null,"abstract":"","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"32 6","pages":"739-739"},"PeriodicalIF":5.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954708","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}