Cancer letters最新文献_第8页

Watershed year of cell and gene therapy (CGT): A review of 2024 CGT approvals 细胞和基因治疗（CGT）的分水岭年：2024年CGT批准的回顾。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-11 DOI: 10.1016/j.canlet.2025.217980

Aiwen Jian , Guo Zhao , Yuning Wang , Shuhang Wang, Ning Li

{"title":"Watershed year of cell and gene therapy (CGT): A review of 2024 CGT approvals","authors":"Aiwen Jian , Guo Zhao , Yuning Wang , Shuhang Wang, Ning Li","doi":"10.1016/j.canlet.2025.217980","DOIUrl":"10.1016/j.canlet.2025.217980","url":null,"abstract":"<div><div>The year 2024 is a pivotal year for therapeutic breakthroughs in human diseases, alongside with an uprising growth in precision medicine, especially in cell and gene therapies (CGTs), marked by an unprecedented approval number of 13 novel CGTs authorized by the U.S. FDA, China's NMPA, E.U. EMA, and Japan's PMDA. 2024 is also a year of many firsts: the first CRISPR therapy, the first MRI-guided intracranial AAV delivery gene therapy, and the first tumor infiltration lymphocyte therapy, opening a whole new chapter of clinical translation of innovations in gene-editing and cell technologies. CGTs represent an emerging translational modality in precision medicine through utilization of cellular or genetic materials to treat or prevent disease, offering curative potential for previously refractory diseases. Despite thriving in CGTs' development, comprehensive analyses of 2024 approvals remain absent. This review employs a quadruple axle comparative framework to analyze 2024-approved CGTs in China and USA, integrating mechanistic innovation with gradually improving regulatory advancements. Raw data was extracted from official agency databases, pivotal trials, and manufacturing reports. This work further delineates how mechanistic diversity converges with regulatory agility to redefine therapeutic development.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"632 ","pages":"Article 217980"},"PeriodicalIF":10.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844467","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

LGR5/mTORC2 axis regulates cellular metabolic plasticity to maintain tumorigenesis in hepatocellular carcinoma. LGR5/mTORC2轴调控肝细胞代谢可塑性，维持肝癌的发生。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-10 DOI: 10.1016/j.canlet.2025.217978

Guishuai Lv, Qianni Zong, Liang Wang, Hongwei Lv, Zixin Wu, Chunying Liu, Suyang Wang, Dan Cao, Hongyang Wang, Wen Yang

{"title":"LGR5/mTORC2 axis regulates cellular metabolic plasticity to maintain tumorigenesis in hepatocellular carcinoma.","authors":"Guishuai Lv, Qianni Zong, Liang Wang, Hongwei Lv, Zixin Wu, Chunying Liu, Suyang Wang, Dan Cao, Hongyang Wang, Wen Yang","doi":"10.1016/j.canlet.2025.217978","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217978","url":null,"abstract":"<p><p>Cancer stem cells (CSCs)/tumor-initiating cells (TICs) withstand metabolic stress and maintain cell survival by means of metabolic reprogramming. However, the underlying mechanisms remain largely unclear. Additionally, it is unknown how to orchestrate metabolic vulnerability of CSCs. LGR5 has been implicated as a CSC marker in colorectal cancer, but in liver cancer, LGR5 has been less studied and its function is not yet explicit. Here, we showed that LGR5 can be used as a marker for liver cancer stem cells (LCSCs), and hepatocellular carcinoma (HCC) cells with high LGR5 expression are more metabolically plastic. In addition, we discovered that LGR5 promotes cancer cell survival by enhancing glycolytic capacity to resist glucose starvation. Mechanistically, LGR5 activates mTORC2 via the RAC1/AKT/FOXO3a axis to induce aerobic glycolysis during metabolic stress. Furthermore, given that p-AMPK was significantly reduced in HCC cells with high expression of LGR5, we found that metformin, an agonist of p-AMPK, inhibits the abnormal phenotypes of HCC cells both in vivo and in vitro by targeting metabolic vulnerabilities. Taken together, these findings establish LGR5 as an important regulator of glycolysis and suggest LGR5 as a potential therapeutic target for LCSCs.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217978"},"PeriodicalIF":10.1,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834057","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

Restricting metabolic plasticity enhances stress adaptation through the modulation of PDH and HIF1A in TRAP1-depleted colon cancer 在trap1缺失的结肠癌中，限制代谢可塑性通过调节PDH和HIF1A来增强应激适应。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-09 DOI: 10.1016/j.canlet.2025.217977

Hong-Yuan Tsai , Miao-Hsueh Chen , Jihye Yun , Lisa A. Lai , John F. Valentine , Mary P. Bronner , Teresa A. Brentnall , Sheng Pan , Ru Chen

{"title":"Restricting metabolic plasticity enhances stress adaptation through the modulation of PDH and HIF1A in TRAP1-depleted colon cancer","authors":"Hong-Yuan Tsai , Miao-Hsueh Chen , Jihye Yun , Lisa A. Lai , John F. Valentine , Mary P. Bronner , Teresa A. Brentnall , Sheng Pan , Ru Chen","doi":"10.1016/j.canlet.2025.217977","DOIUrl":"10.1016/j.canlet.2025.217977","url":null,"abstract":"<div><div>Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation. TRAP1-deficient cells showed tolerance to Oxidative Phosphorylation (OXPHOS) inhibitors and exhibited a higher extracellular acidification rate (ECAR). Additionally, TRAP1 depletion activated hypoxia response elements (HREs) and upregulated HIF1A target genes such as GLUT1 and MCT1. Furthermore, pyruvate dehydrogenase kinases 1 (PDK1) was upregulated in KO cells, leading to the inactivation of the tricarboxylic acid (TCA) cycle enzyme, pyruvate dehydrogenase (PDH). This metabolic shift towards glycolytic metabolism resulted in increased glycolytic metabolism, elevated lactic acid production, and higher glucose consumption, making TRAP1-depleted cancer cells more dependent on this altered metabolism for survival. Treatment with DCA, a PDK inhibitor, restored PDH activity, exacerbated oxidative stress, and increased cell death in KO cells. Our study here sheds light on how TRAP1 depletion affects metabolic plasticity, driving colon cancer cells to adapt to metabolic and oxidative stress. These findings highlight TRAP1 as a promising therapeutic target for manipulating metabolic plasticity and overcoming drug resistance in cancer therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"632 ","pages":"Article 217977"},"PeriodicalIF":10.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820662","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

Altering the gut microbiome and tumor microenvironment in advanced liver cancer: A phase II study of nivolumab, tadalafil and oral vancomycin in patients with refractory primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal or pancreatic cancers 改变晚期肝癌的肠道微生物组和肿瘤微环境：一项尼伏单抗、他达拉非和口服万古霉素治疗难治性原发性肝细胞癌或结直肠癌或胰腺癌的肝显性转移癌的II期研究

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-09 DOI: 10.1016/j.canlet.2025.217975

Chi Ma , Joy A. Awosika , Cecilia Monge , Kelley Coffman-D’Annibale , Changqing Xie , Nebojsa Skorupan , Donna M. Hrones , Meng Liu , Lichun Ma , Bradford J. Wood , Elliot B. Levy , David E. Kleiner , William D. Figg , Bernadette Redd , John A. McCulloch , Miriam R. Fernandes , Giorgio Trinchieri , Tim F. Greten

{"title":"Altering the gut microbiome and tumor microenvironment in advanced liver cancer: A phase II study of nivolumab, tadalafil and oral vancomycin in patients with refractory primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal or pancreatic cancers","authors":"Chi Ma , Joy A. Awosika , Cecilia Monge , Kelley Coffman-D’Annibale , Changqing Xie , Nebojsa Skorupan , Donna M. Hrones , Meng Liu , Lichun Ma , Bradford J. Wood , Elliot B. Levy , David E. Kleiner , William D. Figg , Bernadette Redd , John A. McCulloch , Miriam R. Fernandes , Giorgio Trinchieri , Tim F. Greten","doi":"10.1016/j.canlet.2025.217975","DOIUrl":"10.1016/j.canlet.2025.217975","url":null,"abstract":"<div><div>A phase II study was conducted in patients with primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal (CRC) or pancreatic (PDAC) cancers to assess the effect of nivolumab (anti-PD1), oral vancomycin and tadalafil. Patients were treated with 480 mg nivolumab intravenously every 4 weeks, oral 10 mg tadalafil daily and 125 mg vancomycin orally every 6 h days 1–21 of a 28-day cycle. The primary endpoint was best overall response. Secondary endpoints included analysis of the gut microbiota, serum bile acids and immune cells in peripheral blood. A total of 22 patients were enrolled (6 HCC, 7 CRC and 9 PDAC patients). Three out of 16 evaluable patients (2 patients with HCC and 1 patient with CRC) demonstrated stable disease as best response. No unexpected adverse events were observed. A decrease in secondary bile acids along with changes in gut microbiota were observed. Vancomycin/Tadalafil/Nivolumab treatment did not cause any apparent change of major immune cell frequencies in peripheral blood however, a significant change was observed in monocyte subsets. Treatment was well tolerated and led to changes in the gut microbiome along with changes in the bile acid pool and myeloid cells in peripheral blood. No clinical activity was observed.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"632 ","pages":"Article 217975"},"PeriodicalIF":10.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820628","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

Bimodal silencing of the acinar cell-specific mRNA translation repressor PAIP2B defines a poor prognostic subgroup within the classical pancreatic tumor type 腺泡细胞特异性mRNA翻译抑制因子PAIP2B的双峰沉默定义了典型胰腺肿瘤类型中预后不良的亚组。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-09 DOI: 10.1016/j.canlet.2025.217971

Eulalie Corre , Amandine Alard , Catherine Marbœuf , Charline Lasfargues , Sandra Dailhau , Yuna Blum , Rémy Nicolle , Juan Iovanna , Nelson Dusetti , Stéphane Pyronnet

引用次数: 0

PRMT2 promotes tumorigenic phenotypes through the Wnt signaling pathway and drives immune suppression in Colorectal cancer. PRMT2通过Wnt信号通路促进结直肠癌的致瘤表型并驱动免疫抑制。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-09 DOI: 10.1016/j.canlet.2025.217967

Hailin Zou, Yangruiyu Liu, Xiaoting Yang, Qingyuan Zhang, Qingming Pan, Jiaxin Huang, Yaoyu Guo, Yijun Zhou, Shuo Fang, Zhe-Sheng Chen, Yihang Pan

{"title":"PRMT2 promotes tumorigenic phenotypes through the Wnt signaling pathway and drives immune suppression in Colorectal cancer.","authors":"Hailin Zou, Yangruiyu Liu, Xiaoting Yang, Qingyuan Zhang, Qingming Pan, Jiaxin Huang, Yaoyu Guo, Yijun Zhou, Shuo Fang, Zhe-Sheng Chen, Yihang Pan","doi":"10.1016/j.canlet.2025.217967","DOIUrl":"10.1016/j.canlet.2025.217967","url":null,"abstract":"<p><p>Protein arginine methyltransferase 2 (PRMT2) is a critical epigenetic modulator that orchestrates diverse biological processes through histone methylation-dependent transcriptional regulation. While previous studies have established its pro-inflammatory role in murine colitis, the oncogenic functions and immunomodulatory mechanisms of PRMT2 in colorectal cancer (CRC) pathogenesis remain elusive. In this study, integrated analysis of TCGA database, colorectal cancer single-cell database, and CRC patient-derived tissue microarrays revealed significant upregulation of PRMT2 in tumor tissues, which correlated with adverse clinical outcomes and reduced survival rates. Mechanistically, we found that PRMT2 can promote the transcriptional expression of WNT5A, thereby activating the Wnt/β-catenin signaling pathway and malignant progression of CRC. Notably, our study uncovered the dual immunoregulatory role of PRMT2 in shaping the tumor microenvironment. PRMT2 not only induced M2-like polarization of tumor-associated macrophages (TAMs) but also impaired anti-tumor T cell responses by promoting CD4<sup>+</sup>/CD8<sup>+</sup> T cell dysfunction. In conclusion, our findings position PRMT2 as a multifaceted therapeutic target that simultaneously addresses tumor intrinsic malignancy and microenvironmental immunosuppression in CRC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217967"},"PeriodicalIF":10.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793565","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

SEED: A novel method for identifying cancer prognosis target genes without control samples SEED：一种无需对照样本识别癌症预后靶基因的新方法。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-07 DOI: 10.1016/j.canlet.2025.217960

Hao-Xu Yang , Xiao Gao , Hui-Juan Zhong , Yao Qin , Jie Xiong , Wei-Li Zhao

引用次数: 0

Organoids in the research of pancreatic neoplasms: cultivation, applications, and limitations 类器官在胰腺肿瘤研究中的应用：培养、应用和局限性。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-07 DOI: 10.1016/j.canlet.2025.217968

Changwei Du , Yueze Liu , Xiaoyue Lu , Menggang Zhang, Shijuan Jiang, Zhe Cao, Gang Yang, Jiangdong Qiu, Taiping Zhang, Yupei Zhao

{"title":"Organoids in the research of pancreatic neoplasms: cultivation, applications, and limitations","authors":"Changwei Du , Yueze Liu , Xiaoyue Lu , Menggang Zhang, Shijuan Jiang, Zhe Cao, Gang Yang, Jiangdong Qiu, Taiping Zhang, Yupei Zhao","doi":"10.1016/j.canlet.2025.217968","DOIUrl":"10.1016/j.canlet.2025.217968","url":null,"abstract":"<div><div>Pancreatic neoplasms are mainly classified as pancreatic ductal adenocarcinoma (PDAC), pancreatic neuroendocrine neoplasms, and pancreatic cystic neoplasms. As a three-dimensional <em>in vitro</em> culture model, organoid technology can faithfully mimic the tissue structure, cell types, and tumor microenvironment, providing an innovative tool for pancreatic neoplasm research. This review systematically summarizes the application progress and challenges of organoid technology in pancreatic neoplasms research. At the methodological level, organoid models are constructed through techniques such as Matrigel embedding, air-liquid interface, microfluidic chips, and suspension culture. These models preserve the molecular characteristics and heterogeneity of neoplasms, effectively addressing the limitations of traditional models, such as long cultivation periods and significant species differences. In terms of research applications, organoid technology has been widely used for omics analysis, drug screening, and the simulation of the tumor microenvironment in PDAC studies. The review underscores recent advances in these areas, with a focus on key research findings and ongoing clinical trials. Despite its advantages, organoid technology still encounters several limitations: the progressive loss of tumor microenvironment components, heavy reliance on Matrigel, challenges in obtaining sufficient and representative patient samples, inter-sample heterogeneity, non-neoplastic cell contamination, and the current lack of standardized culture protocols. In conclusion, by accurately replicating the biological characteristics of tumors, organoid technology has emerged as a powerful platform that has significantly advanced both basic research and clinical treatments for pancreatic neoplasms.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"632 ","pages":"Article 217968"},"PeriodicalIF":10.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811836","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

Machine perfusion prevents early tumor recurrence in liver transplantation for hepatocellular carcinoma: a multicenter retrospective cohort study 机器灌注预防肝癌肝移植早期肿瘤复发：一项多中心回顾性队列研究

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-07 DOI: 10.1016/j.canlet.2025.217970

Wenzhi Shu , Hao Chen , Ruolin Wang , Jiyong Song , Rui Tang , Guangdong Wu , Lihan Yu , Xuan Tong , Xiaojuan Wang , Yucheng Hou , Wen long Zhao , Lizhen Zhu , Jun Yan , Qian Lu

{"title":"Machine perfusion prevents early tumor recurrence in liver transplantation for hepatocellular carcinoma: a multicenter retrospective cohort study","authors":"Wenzhi Shu , Hao Chen , Ruolin Wang , Jiyong Song , Rui Tang , Guangdong Wu , Lihan Yu , Xuan Tong , Xiaojuan Wang , Yucheng Hou , Wen long Zhao , Lizhen Zhu , Jun Yan , Qian Lu","doi":"10.1016/j.canlet.2025.217970","DOIUrl":"10.1016/j.canlet.2025.217970","url":null,"abstract":"<div><div>There is controversy regarding whether the machine perfusion (MP) prevents hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to explore the impact of MP on HCC recurrence. We included data from the United Network for Organ Sharing (UNOS) database on HCC patients spanning from April 2015 and January 2024. Patients who received MP-preserved donor were propensity score-matched (PSM) 1:1 with those who received static cold storage (SCS)-preserved donor. The primary outcome was recurrence-free survival (RFS) rate. Cox regression models were used to identify predictors of RFS. Subgroup analyses assessed the role of MP across various groups and to identify the beneficial group. The PSM cohort comprised 411 HCC recipients with MP-preserved donors and 411 with SCS-preserved donors. The 2-year RFS rate was significantly higher in the MP group compared to the SCS group (96.5 % vs. 89.7 %, P = 0.008). Univariate and multivariate Cox regression analyses revealed that MP preservation method was an independent predictor of RFS [adjusted hazard ratio (aHR), 0.158; 95 % confidence interval (CI), 0.048–0.523; P = 0.003]. In the beneficial group, defined by the cumulative of MP-enhancing factors, MP improved RFS comparable to SCS group (96.7 % vs. 76.2 %, P = 0.001). MP effectively prevents HCC recurrence post-LT. MP should be used more proactively in the beneficial groups, including those with hemodynamically unstable donors and high tumor burden, to improve the survival outcomes.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"633 ","pages":"Article 217970"},"PeriodicalIF":10.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811835","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

Advances in extracellular Vesicle-based cancer precision medicine 基于细胞外囊泡的肿瘤精准医学研究进展。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-08-06 DOI: 10.1016/j.canlet.2025.217976

Hema Saranya Ilamathi , Gina Rinaldo , Oscar P.B. Wiklander

引用次数: 0