Cancer letters最新文献

Corrigendum to "FUT2-dependent fucosylation of LAMP1 promotes the apoptosis of colorectal cancer cells by regulating theautophagy-lysosomal pathway" [Cancer Lett. (2025) 619 217643]. “fut2依赖的LAMP1聚焦通过调节自噬-溶酶体途径促进结直肠癌细胞凋亡”的更正[cancer Lett]。（2025） 619 217643]。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-10-03 DOI: 10.1016/j.canlet.2025.217981

Zijun Guo, Lingnan He, Weijun Wang, Shuxin Tian, Rong Lin

引用次数: 0

Targeting the FBXO5-DOK6 Axis to Overcome Temozolomide Resistance in Glioblastoma via Proteasome-Cytomechanics Regulation. 通过蛋白酶体-细胞力学调控靶向FBXO5-DOK6轴克服胶质母细胞瘤替莫唑胺耐药性

IF 10.1 1区医学

Cancer letters Pub Date : 2025-10-02 DOI: 10.1016/j.canlet.2025.218072

Chao Wang, Mengqi Wang, Zhenye Zhu, Huang Tan, Danchen Su, Mu Qiao, Mingru Jiang, Fengyuan Che

{"title":"Targeting the FBXO5-DOK6 Axis to Overcome Temozolomide Resistance in Glioblastoma via Proteasome-Cytomechanics Regulation.","authors":"Chao Wang, Mengqi Wang, Zhenye Zhu, Huang Tan, Danchen Su, Mu Qiao, Mingru Jiang, Fengyuan Che","doi":"10.1016/j.canlet.2025.218072","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.218072","url":null,"abstract":"<p><p>The development of resistance to temozolomide (TMZ) represents a critical challenge in the management of glioblastoma (GBM), yet the molecular basis for this resistance is still not fully elucidated. In this study, we utilized a custom-designed CRISPR/Cas9 sgRNA library that targets 1,117 genes associated with ubiquitination, combined with a positive-negative dual screening strategy, to identify pivotal factors in TMZ resistance. This approach revealed F-Box Protein 5 (FBXO5), an E3 ligase subunit, as a major contributor to TMZ resistance. Correlation analyses indicated that high levels of FBXO5 are associated with poor treatment response and reduced survival in GBM patients. Further investigation showed that FBXO5 promotes K48-linked polyubiquitination and subsequent proteasomal breakdown of DOK6, a protein whose depletion enhances mechanical rigidity in tumor cells and initiates survival signaling. Additionally, through virtual screening of a natural product library containing 4,500 compounds, we identified Theaflavin 3,3'-digallate (TF3) as a selective inhibitor of FBXO5. This compound was found to synergistically improve TMZ sensitivity both in vitro and in vivo. Our results highlight a critical proteasome-cytomechanics pathway in GBM chemoresistance and suggest that targeting FBXO5 could be an effective therapeutic strategy for treating patients with GBM.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218072"},"PeriodicalIF":10.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The Actin Histidine methyltransferase SETD3 is a CHD1 lysine di-methyltransferase 肌动蛋白组氨酸甲基转移酶SETD3是一种CHD1赖氨酸二甲基转移酶

IF 10.1 1区医学

Cancer letters Pub Date : 2025-10-02 DOI: 10.1016/j.canlet.2025.218073

Weilin Peng , Christopher Wang , Rui Yang , Xiong Peng , Zhenyu Zhao , Boxue He , Bei Qing , Qidong Cai , Wei Yin , Yichuan Chen , Fenglei Yu , Xiang Wang , Yongguang Tao

引用次数: 0

Irreversible electroporation with intratumoral plant virus immunotherapy induces systemic immunity in a metastatic model of pancreatic cancer. 不可逆电穿孔与肿瘤内植物病毒免疫治疗诱导胰腺癌转移模型的全身免疫。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-10-02 DOI: 10.1016/j.canlet.2025.218074

Debbie K Ledezma, Utsav Joshi, Kim Nguyen-Ta, Himangshu Sonowal, Hanna Russo, Isabel G Newton, Nicole F Steinmetz, Rebekah R White

{"title":"Irreversible electroporation with intratumoral plant virus immunotherapy induces systemic immunity in a metastatic model of pancreatic cancer.","authors":"Debbie K Ledezma, Utsav Joshi, Kim Nguyen-Ta, Himangshu Sonowal, Hanna Russo, Isabel G Newton, Nicole F Steinmetz, Rebekah R White","doi":"10.1016/j.canlet.2025.218074","DOIUrl":"10.1016/j.canlet.2025.218074","url":null,"abstract":"<p><p>Pancreatic cancer remains highly resistant to immunotherapy, necessitating innovative strategies. This study explores a novel combination of irreversible electroporation (IRE) and plant virus-based nanoparticles to enhance immune responses in pancreatic ductal adenocarcinoma (PDAC). IRE is a non-thermal tumor ablation technique already in clinical use, but it often fails to prevent metastasis. Plant viral nanoparticles, such as cowpea mosaic virus (CPMV), have shown potent immune-stimulating properties in various cancer models. Using an immunocompetent orthotopic PDAC mouse model with liver metastases, we evaluated the impact of combining IRE and intratumoral CPMV. Combination therapy significantly improved survival and increased infiltration of activated, profilerating CD8<sup>+</sup> T cells compared to either treatment alone. Notably, liver metastases from treated mice also showed elevated CD8<sup>+</sup> T and NK cell infiltration. Further, lymph node analysis revealed enhanced dendritic cell maturation and expansion of CD8<sup>+</sup> effector memory T cells. These results suggest that IRE and CPMV synergize to generate robust local and systemic anti-tumor immunity. This combinatorial strategy effectively converts immunologically \"cold\" tumors into \"hot\" tumors, offering a promising approach that can be feasibly translated to PDAC patients.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218074"},"PeriodicalIF":10.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Loss of ADAR1 in lung cancer activates anti-tumour immunity and suppresses tumour cell growth via the RIG-I/MDA5-MAVS pathway. 肺癌中ADAR1的缺失通过RIG-I/MDA5-MAVS途径激活抗肿瘤免疫并抑制肿瘤细胞生长。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-30 DOI: 10.1016/j.canlet.2025.218071

Wenxiao Jia, Lin Ma, Menglin Bai, Ji Li, Peng Jin, Min Wang, Jiatong Li, Xiaokang Guo, Yaru Tian, Hongbo Guo, Jinming Yu, Hui Zhu

{"title":"Loss of ADAR1 in lung cancer activates anti-tumour immunity and suppresses tumour cell growth via the RIG-I/MDA5-MAVS pathway.","authors":"Wenxiao Jia, Lin Ma, Menglin Bai, Ji Li, Peng Jin, Min Wang, Jiatong Li, Xiaokang Guo, Yaru Tian, Hongbo Guo, Jinming Yu, Hui Zhu","doi":"10.1016/j.canlet.2025.218071","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.218071","url":null,"abstract":"<p><p>Aberrant accumulation of dsDNA in tumour cells activates the cGAS-STING pathway, playing a crucial role in anti-tumour immunity. However, the role of the dsRNA sensor RIG-I-like receptor-mitochondrial antiviral signalling protein (RLR-MAVS) in anti-tumour immunity remains unclear. ADAR1 edits endogenous dsRNA by catalysing the deamination of adenosine to inosine, preventing activation of the RLR-MAVS pathway, which is vital for immune homeostasis and tissue development. In this study, we investigated the roles of ADAR1 and RLR-MAVS in anti-tumour immunity of lung cancer. Our findings revealed that knockout Adar1 induces dsRNA accumulation, activating the TBK1-IRF3 pathway and stimulating interferon stimulating genes (ISGs) expression, which in turn activates anti-tumour immunity and suppresses lung cancer growth. We demonstrated that the RIG-I/MDA5-MAVS pathway is responsible for this anti-tumour immune activation and tumour suppression, which is contrast to the effects mediated by Zbp1, another downstream molecule regulated by Adar1, which is known to drive lethal type I interferon activation and immunopathology inflammatory responses. Moreover, we found that Adar1-deficient lung cancer cells suppress abscopal homogeneous and non-homogeneous tumour growth when used as a tumour cell vaccine. Additionally, Adar1 deficiency in lung cancer cells significantly enhances the efficacy of immunotherapy when employed as adjuvant. In summary, our study elucidates the mechanism by which Adar1 deficiency activates anti-tumour immunity and inhibits tumour cell growth. These findings highlight Adar1 and the downstream RIG-I/MDA5-MAVS pathway as promising targets for immunotherapy development.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218071"},"PeriodicalIF":10.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The neuro-immune oncology axis 神经免疫肿瘤学轴。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-29 DOI: 10.1016/j.canlet.2025.218070

Fabien Vanden Abeele , Michel Salzet

{"title":"The neuro-immune oncology axis","authors":"Fabien Vanden Abeele , Michel Salzet","doi":"10.1016/j.canlet.2025.218070","DOIUrl":"10.1016/j.canlet.2025.218070","url":null,"abstract":"<div><div>Cancer was long viewed primarily as a genetic disease of uncontrolled cellular proliferation. However, emerging evidence highlights the crucial influence of the tumor microenvironment, particularly the interplay between the nervous and immune systems, in driving cancer progression. Recent discoveries, notably the migration of neural progenitor cells from the central nervous system (CNS) to peripheral tumors, introduce a paradigm wherein neural stem cells actively contribute to tumor initiation and progression. In this framework, CNS-derived neural progenitors infiltrate developing tumors, establish new neural networks, and engage in bidirectional communication with immune cells via neuronal signaling molecules (neurotransmitters, neuropeptides, and even ion channels such as ORAI3 and TRPV1). Here we review the detailed molecular and cellular mechanisms underlying this neuro-immune axis in cancer, emphasizing how neurotransmitter signaling, neuropeptide release, and specialized ion channels mediate cross-talk between nerves, immune cells, and malignant cells. We examine these interactions in the context of specific cancers prostate, breast, lung, and pancreatic to illustrate how neural inputs shape immune evasion and tumor progression in each setting. The clinical relevance of neuro-immune crosstalk is discussed, including evidence that tumor innervation correlates with prognosis and can modulate responses to therapy. Finally, we outline emerging therapeutic strategies targeting neural–immune interactions, such as neuromodulatory drugs and nerve-stimulation interventions, which hold promise for enhancing antitumor immunity. By synthesizing these recent insights, we propose a novel view of cancer as a disease of disrupted neuro-immune communication and highlight opportunities to exploit this axis for improved cancer treatment.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"634 ","pages":"Article 218070"},"PeriodicalIF":10.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Targeting inosine metabolism to enhance EGFR-targeted therapy in lung adenocarcinoma 靶向肌苷代谢增强egfr在肺腺癌中的靶向治疗。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-29 DOI: 10.1016/j.canlet.2025.218069

Xiaolong Huang , Jiaqi Liang , Yanjun Yi , Junkan Zhu, Han Lin, Shencheng Ren, Tao Cheng, Guoshu Bi, Guangyao Shan, Dejun Zeng, Fengkai Xu, Di Ge, Cheng Zhan

{"title":"Targeting inosine metabolism to enhance EGFR-targeted therapy in lung adenocarcinoma","authors":"Xiaolong Huang , Jiaqi Liang , Yanjun Yi , Junkan Zhu, Han Lin, Shencheng Ren, Tao Cheng, Guoshu Bi, Guangyao Shan, Dejun Zeng, Fengkai Xu, Di Ge, Cheng Zhan","doi":"10.1016/j.canlet.2025.218069","DOIUrl":"10.1016/j.canlet.2025.218069","url":null,"abstract":"<div><div>Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for treating EGFR-mutant lung adenocarcinoma (LUAD), resistance significantly impairs their therapeutic effect. In this study, we explored the metabolic features associated with EGFR-TKI resistance and identified the nucleoside inosine as being significantly accumulated in TKI-resistant cells, drug-tolerant persister (DTP) cells, and clinical TKI-residual tumors. Mechanically, accumulated inosine activated the adenosine A<sub>2A</sub> receptor (A2aR) and the cAMP-PKA-CREB signaling pathway, thereby enhancing oxidative phosphorylation and TKI resistance. Additionally, we identified that inosine secreted by TKI-resistant cells also induced M2-like reprogramming of macrophages. Downregulated purine nucleotide phosphorylase (PNP) was identified as the pivotal factor for the accumulation of inosine. Overexpression of PNP in TKI-resistant cells not only increased sensitivity of TKI-resistant cells to EGFR-TKIs, but also induced cell death by elevating toxic xanthine, uric acid, and ROS production. Furthermore, overexpression of PNP or using taminadenant, a A2aR-targeting inhibitor used in clinical trials, significantly enhances the EGFR-targeted therapeutic response <em>in vitro</em>, as well as in patient-derived organoids, cell-derived xenografts and mouse models bearing human EGFR-driven spontaneous lung tumor. Overall, our findings clarify the role of inosine metabolism in TKI resistance, highlighting a potential therapeutic strategy—targeting the inosine/A2aR axis—to counteract EGFR-TKI tolerance in LUAD treatment.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"634 ","pages":"Article 218069"},"PeriodicalIF":10.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

STAT3 induced BRD9 activation promotes intrahepatic cholangiocarcinoma progression by enhancing CD36 controlled fatty acid metabolism. STAT3诱导的BRD9激活通过增强CD36控制的脂肪酸代谢促进肝内胆管癌的进展。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-29 DOI: 10.1016/j.canlet.2025.218066

Yichao Bu, Diyu Chen, Jie Li, Rui Yang, Jun Gao, Weifeng Qu, Xiutao Fu, Weiren Liu, Zhenbin Ding, Jian Zhou, Yinghong Shi, Jia Fan, Yuan Fang, Zheng Tang

{"title":"STAT3 induced BRD9 activation promotes intrahepatic cholangiocarcinoma progression by enhancing CD36 controlled fatty acid metabolism.","authors":"Yichao Bu, Diyu Chen, Jie Li, Rui Yang, Jun Gao, Weifeng Qu, Xiutao Fu, Weiren Liu, Zhenbin Ding, Jian Zhou, Yinghong Shi, Jia Fan, Yuan Fang, Zheng Tang","doi":"10.1016/j.canlet.2025.218066","DOIUrl":"10.1016/j.canlet.2025.218066","url":null,"abstract":"<p><p>Intrahepatic cholangiocarcinoma (ICC) is an aggressive bile-duct malignancy with high mortality rates, poor sensitivity to chemotherapy, and poor prognosis. Treatment options are extremely limited. Bromodomain-containing protein 9 (BRD9) has been linked to the development of various cancers, and therapies targeting BRD9 have been found to be effective. However, the role of BRD9 in ICC has not been examined, and the mechanism underlying the effects of BRD9 in cancer remain unknown. In this study, we investigated the association between BRD9 expression and ICC tumor progression, finding that high levels of BRD9 were linked to ICC tumor growth and unfavorable prognosis. In terms of the mechanism, the STAT3-BRD9-CD36 axis was found to be involved in ICC tumor growth. High BRD9 expression was found to promote CD36 expression, enhancing fatty acid metabolism in tumor cells to enable more rapid proliferation, and high BRD9 levels were influenced by elevated STAT3 expression. Treatment with the CPT1A inhibitor Etomoxir further confirmed this mechanism by blocking lipid transfer into the mitochondria and suppressing fatty acid oxidation, resulting in lipid accumulation. In addition, it was found that inhibition of BRD9 reduced ICC tumor growth and could help overcome chemoresistance. Together, the results suggest the potential of BRD9 as a therapeutic target for intrahepatic cholangiocarcinoma and highlight its role in regulating fatty acid metabolism in cancer cells.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218066"},"PeriodicalIF":10.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Corrigendum to "Inhibition of Aurora kinases induces apoptosis and autophagy via AURKB/p70S6K/RPL15 axis in human leukemia cells" [Cancer. Lett. (382) 2016-11-28; 382(2):215-230]. “抑制极光激酶通过AURKB/p70S6K/RPL15轴诱导人类白血病细胞凋亡和自噬”的更正[癌症]。列托人。(382) 2016-11-28;382(2): 215 - 230)。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-27 DOI: 10.1016/j.canlet.2025.218039

Si-Jia He, Li-Ping Shu, Zhi-Wei Zhou, Tianxin Yang, Wei Duan, Xueji Zhang, Zhi-Xu He, Shu-Feng Zhou

引用次数: 0

Developmental checkpoint targeting: Pre-TCR immunotherapy in leukemia and beyond. 发育检查点靶向：白血病及其他疾病的tcr前免疫治疗。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-26 DOI: 10.1016/j.canlet.2025.218063

Wenxue Ma, Catriona Jamieson

引用次数: 0