Cancer letters最新文献_第8页

YAP/TAZ: An epitome of tumorigenesis YAP/TAZ：肿瘤发生的一个缩影。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-15 DOI: 10.1016/j.canlet.2025.217806

Soumya Mukherjee, Emily A. Warden, Jianmin Zhang

{"title":"YAP/TAZ: An epitome of tumorigenesis","authors":"Soumya Mukherjee, Emily A. Warden, Jianmin Zhang","doi":"10.1016/j.canlet.2025.217806","DOIUrl":"10.1016/j.canlet.2025.217806","url":null,"abstract":"<div><div>Mounting evidence has demonstrated that the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are the main effectors of the Hippo signal transduction pathway that is involved in multiple layered events in tumorigenesis. The role of YAP/TAZ in cancer development is critical in a context dependent manner. Overexpression of YAP/TAZ induces cell proliferation and is elevated in various cancers and many other malignancies. On the other hand, studies have shown YAP binds p73 to activate PML transcription in response to DNA damage and generate a DNA-damage-induced feedback loop. Intriguingly, at the genomic level, YAP/TAZ genes are rarely mutated in cancer, except in specific tumors. The central role of YAP/TAZ in driving tumorigenesis is attributed through diverse mechanisms, such as regulatory kinases, cellular mechano-transduction, epigenetic modification/alterations, post-translational modifications, protein -protein interaction and nucleo-cytoplasmic export import. The complex interplay among feedback loops and crosstalk between various signaling pathways portrays the dynamic nature of YAP/TAZ. Thus, a comprehensive understanding of how posttranslational modifications and nucleo-cytoplasmic traffic of YAP/TAZ dynamically regulate and control each other holds great promise for selectively targeting YAP/TAZ import and export for drug therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217806"},"PeriodicalIF":9.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092864","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 “Selective degradation of FGFR1/2 overcomes antiestrogen resistance in ER+ breast cancer with FGFR1/2 alterations” [619 1 (2025) 217668 1–13]

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-14 DOI: 10.1016/j.canlet.2025.217782

Yasuaki Uemoto , Chang-Ching A Lin , Bingnan Wang , Dan Ye , Yisheng V. Fang , Emmanuel Bikorimana , Fabiana Napolitano , Maria Rosario Chica-Parrado , Cheung Li , Saurabh Mendiratta , Chuo Chen , Ariella B. Hanker , Carlos L. Arteaga

引用次数: 0

Keloids revisited: Current concepts in treatment and differential diagnosis 瘢痕疙瘩重述：当前治疗和鉴别诊断的概念。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-14 DOI: 10.1016/j.canlet.2025.217802

Yanhui Liu , Xiao Chen , Katharina S. Fischer , Siqi Fu , Li Yuan , Xing Hu

{"title":"Keloids revisited: Current concepts in treatment and differential diagnosis","authors":"Yanhui Liu , Xiao Chen , Katharina S. Fischer , Siqi Fu , Li Yuan , Xing Hu","doi":"10.1016/j.canlet.2025.217802","DOIUrl":"10.1016/j.canlet.2025.217802","url":null,"abstract":"<div><div>Keloid is a special type of scar considered prototypic of skin fibrosis. Unlike hypertrophic scars, keloids exceed the margins of the original wound, and exist over time without a quiescent or regressive phase. Although keloids do not metastasize, they exhibit tumor-like characteristics, and share many similarities. Large epidemiological study demonstrates that patients with keloids have a 1.49-fold higher risk for cancers. Keloids can lead to severe functional impairments and diminish quality of life which increases hidden costs for patients and medical systems. The main goals of treatments are to improve scar appearance, symptoms and patient's quality of life (QoL). However, the microenvironment, pathogenesis, formation and development of the keloid are complex, the efficacy of multiple treatments were limited. Therefore, this up-to-date review aimed to target the current concepts in keloid treatment and differential diagnosis. The goal is to provide a reference for doctors and researchers to improve the accuracy of diagnosis and facilitate the selection of personalized treatment methods for patients with keloids.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217802"},"PeriodicalIF":9.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076208","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

Patient-derived organoid co-culture systems as next-generation models for bladder cancer stem cell research 患者源性类器官共培养系统作为膀胱癌干细胞研究的下一代模型。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-12 DOI: 10.1016/j.canlet.2025.217793

Ruici Yang , Shanzhao Wang , Zhichao Li , Cong Yin , Wei Huang , Weiren Huang

{"title":"Patient-derived organoid co-culture systems as next-generation models for bladder cancer stem cell research","authors":"Ruici Yang , Shanzhao Wang , Zhichao Li , Cong Yin , Wei Huang , Weiren Huang","doi":"10.1016/j.canlet.2025.217793","DOIUrl":"10.1016/j.canlet.2025.217793","url":null,"abstract":"<div><div>Three-dimensional patient-derived organoids (PDOs) have emerged as a powerful model for investigating the molecular and cellular mechanisms underlying bladder cancer, particularly in the context of cancer stem cells (CSCs) and drug screening. However, a significant limitation of conventional PDOs is the absence of tumor microenvironment (TME), which includes critical stromal, immune and microbial components that influence tumor behavior and treatment response. In this review, we provide a comprehensive overview of the recent advancements in PDO co-culture systems designed to integrate TME elements. Additionally, we emphasize the role of biomedical engineering technologies, such as 3D bioprinting and organoids-on-a-chip, in enhancing the physiological relevance of these models. Furthermore, we explore how bladder PDO co-culture systems are applied in research on bladder CSC characterization, evolution and treatment responses. Finally, we discuss future directions for improving PDO systems to achieve more accurate preclinical modeling and drug discovery.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"625 ","pages":"Article 217793"},"PeriodicalIF":9.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076210","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

Efficacy and safety of inetetamab plus pertuzumab and nab-paclitaxel as neoadjuvant therapy for HER2+ breast cancer: A single-arm multicenter phase II clinical trial 一项单臂多中心II期临床试验：inetetamab联合pertuzumab和nab-紫杉醇作为HER2+乳腺癌新辅助治疗的疗效和安全性

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-10 DOI: 10.1016/j.canlet.2025.217785

Wen-Jia Zuo , Lin-xiao-xi Ma , Zhi-hong Wang , Xu-chen Cao , Xin-jian Jia , Wen-he Zhao , Ming-liang Zhang , Hong-wei Yang , Mao-shan Chen , Jing Wang , Xiao-yu Liu , Hao Zhang , Xiu-chun Chen , Dong Song , Hao Wang , Xiao-peng Ma , Ya-Bing Wang , Hao Yu , Zhong-Hua Wang , Zhi-Ming Shao

{"title":"Efficacy and safety of inetetamab plus pertuzumab and nab-paclitaxel as neoadjuvant therapy for HER2+ breast cancer: A single-arm multicenter phase II clinical trial","authors":"Wen-Jia Zuo , Lin-xiao-xi Ma , Zhi-hong Wang , Xu-chen Cao , Xin-jian Jia , Wen-he Zhao , Ming-liang Zhang , Hong-wei Yang , Mao-shan Chen , Jing Wang , Xiao-yu Liu , Hao Zhang , Xiu-chun Chen , Dong Song , Hao Wang , Xiao-peng Ma , Ya-Bing Wang , Hao Yu , Zhong-Hua Wang , Zhi-Ming Shao","doi":"10.1016/j.canlet.2025.217785","DOIUrl":"10.1016/j.canlet.2025.217785","url":null,"abstract":"<div><div>The combination of inetetamab and vinorelbine has demonstrated survival benefits with an acceptable toxicity profile in HER2+ metastatic breast cancer (MBC) patients. This multicenter, single-arm, phase II trial further evaluates the efficacy of inetetamab combined with pertuzumab and nab-paclitaxel as neoadjuvant therapy. Treatment-naïve patients with HER2+ early-stage or locally advanced BC received four cycles of intravenous inetetamab (8 mg/kg loading dose, then 6 mg/kg for subsequent doses), intravenous pertuzumab (840 mg loading dose, then 420 mg for subsequent doses), and weekly nab-paclitaxel (125 mg/m<sup>2</sup>). The primary endpoint was the total pathological complete response (tpCR) rate, defined as ypT0/is and ypN0, assessed by independent central review. From March 2023 to February 2024, 62 patients were enrolled, with the majority (61/62) completing 4 cycles of neoadjuvant therapy. The tpCR rate was 56.5 % (95 % CI: 43.3 %–69.0 %). Further analysis showed that patients with estrogen receptor (ER) negative tumors derived greater benefit, with a tpCR rate of 90.9 %. The objective response rate was 90.3 % (95 % CI: 80.1 %–96.4 %). The most common grade 3 or higher adverse events were neutropenia (32.3 %), decreased white blood cell count (19.4 %), infectious pneumonia (3.2 %), anemia (3.2 %), and diarrhea (3.2 %). No death occurred during the neoadjuvant treatment. Neoadjuvant treatment with inetetamab, in combination with pertuzumab and nab-paclitaxel, demonstrates good efficacy and tolerability, especially in ER-negative patients.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"627 ","pages":"Article 217785"},"PeriodicalIF":9.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975224","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

Association of CMV status with response to neoadjuvant chemoimmunotherapy in early triple-negative breast cancer 巨细胞病毒状态与早期三阴性乳腺癌新辅助化疗免疫治疗反应的关系

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-10 DOI: 10.1016/j.canlet.2025.217789

Vincent Walter , André Koch , Dorothea Hillmann , Dominik Dannehl , Annette Staebler , Kerstin Pfister , Lorenz Risch , Tobias Engler , Sara Brucker , Wolfgang Janni , Andreas Hartkopf , Lukas Flatz

引用次数: 0

Activated Schwann cells promote tumor growth in colon cancer 活化的雪旺细胞促进结肠癌肿瘤生长

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-10 DOI: 10.1016/j.canlet.2025.217791

Kexin He , Hao Wang , Hao Wu , Weihan Li , Ruixue Huo , Luju Jiang , Minhao Yu , Junli Xue

{"title":"Activated Schwann cells promote tumor growth in colon cancer","authors":"Kexin He , Hao Wang , Hao Wu , Weihan Li , Ruixue Huo , Luju Jiang , Minhao Yu , Junli Xue","doi":"10.1016/j.canlet.2025.217791","DOIUrl":"10.1016/j.canlet.2025.217791","url":null,"abstract":"<div><div>Schwann cells, traditionally recognized as glial cells of the peripheral nervous system, have emerged as pivotal cellular constituents within the tumor microenvironment. Colon cancer exhibits significant nerve dependence; however, the roles of Schwann cells in colon cancer progression remain insufficiently understood. Here, we identified a significant increase in tumor-associated nonmyelinating Schwann cells within colon tumor samples compared to their normal tissue counterparts. Furthermore, the elevated abundance of these cells was associated with poorer clinical outcomes in colon cancer. Within colon tumor tissues, Schwann cells displayed elevated expression of c-Jun, a key gene involved in their activation and reprogramming. Knocking down c-Jun hampered Schwann cell activation. Single-cell RNA sequencing analysis uncovered that glial cells engage in the most robust cell-cell interactions with malignant cells and fibroblasts. Co-culture experiments demonstrated that tumor cells and cancer-associated fibroblasts specifically promoted c-Jun activation in Schwann cells, whereas co-culture with immune cells did not elicit a similar response. Under <em>In vivo</em> conditions, Schwann cells enhance tumor growth in a c-Jun-dependent manner. Moreover, c-Jun knockout in Schwann cells orchestrated a reprogramming of their secretome, exemplified by a notable reduction in IL-6, a key effector of their tumor-promoting activity. Collectively, our study elucidates the critical role of activated Schwann cells in colon cancer, which may offer a novel therapeutic strategy for treatment.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"626 ","pages":"Article 217791"},"PeriodicalIF":9.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935279","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

A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC PP2A-mtATR-tBid轴将DNA损伤诱导的CIP2A降解与PDAC的凋亡休眠和治疗抗性联系起来。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-10 DOI: 10.1016/j.canlet.2025.217790

Yibo Luo, Himadri Biswas, Yetunde Makinwa, Shi-He Liu, Zizheng Dong, Jing-Yuan Liu, Jian-Ting Zhang, Yue Zou

{"title":"A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC","authors":"Yibo Luo, Himadri Biswas, Yetunde Makinwa, Shi-He Liu, Zizheng Dong, Jing-Yuan Liu, Jian-Ting Zhang, Yue Zou","doi":"10.1016/j.canlet.2025.217790","DOIUrl":"10.1016/j.canlet.2025.217790","url":null,"abstract":"<div><div>DNA damage-based drugs are widely used in cancer therapy, yet resistance remains a major challenge. In this study, we uncovered a non-DNA repair mechanism contributing to resistance in pancreatic ductal adenocarcinoma (PDAC). We show that in gemcitabine-resistant PDAC cells, CIP2A undergoes ubiquitin-mediated degradation, resulting in enhanced PP2A phosphatase activity. This leads to the dephosphorylation of ATR at Ser428 in the cytoplasm, promoting the formation of the prolyl <em>cis</em>-isomeric form of ATR at its Ser428-Pro429 motif. The resulting <em>cis</em>-ATR functions as a mitochondria-targeted antiapoptotic protein (mtATR). Surprisingly, resistant PDAC cells paradoxically accumulated both mtATR and proapoptotic tBid at the mitochondria, forming a stable mtATR-tBid complex that induces a state of apoptotic dormancy. Disrupting this complex, either with the PP2A inhibitor LB-100 or a cytoplasmic ATR-specific antibody, reactivates the pre-accumulated tBid and restores apoptosis in resistant PDAC cells. In an orthotopic PDAC mouse model, LB-100 alone significantly inhibit gemcitabine-resistant tumor growth by disrupting the mtATR-tBid complex. These findings reveal a previously unrecognized mechanism of resistance to DNA damage-based therapies and identify a novel action mechanism of LB-100, characterized by the CIP2A degradation-mediated PP2A-mtATR-tBid axis. By targeting mtATR-tBid-mediated apoptotic dormancy, this strategy offers a promising approach to restore apoptotic sensitivity in drug-resistant cancers.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"627 ","pages":"Article 217790"},"PeriodicalIF":9.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975143","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 “CircMFN2/miR-361-3p/ELK1 feedback loop promotes glutaminolysis and the progression of hepatocellular carcinoma” [Cancer Lett. 614 (2025) 217473] “CircMFN2/miR-361-3p/ELK1反馈回路促进谷氨酰胺溶解和肝细胞癌的进展”的勘误表[Cancer Lett] . 614 (2025) 217473]

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-10 DOI: 10.1016/j.canlet.2025.217755

Xiaopei Hao , Xiangjun Qian , Chenxi Xie , Zhengzheng Wang , Xiaoqian Wang , Yang Ji , Xiaokai Zhang , Qingjun Li , Baishun Wan , Hong Cui , Li Wang , Nanmu Yang , Liang Qiao , Haibo Yu , Feng Han , Hao Zhuang , Jinxue Zhou

引用次数: 0

Targeting of COPⅠ elicits CD8+ T cell-mediated anti-tumor immunity and suppresses growth of intrahepatic cholangiocarcinoma

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-08 DOI: 10.1016/j.canlet.2025.217786

Zehong Chen , Guiqin Xu , Chen Xu , Yun Liu , Zhaojuan Yang , Lvzhu Xiang , You Zuo , Ningqian Zheng , Zhiqian Ye , Wangjie Xu , Yingbin Liu , Yongzhong Liu , Li Zhang

{"title":"Targeting of COPⅠ elicits CD8+ T cell-mediated anti-tumor immunity and suppresses growth of intrahepatic cholangiocarcinoma","authors":"Zehong Chen , Guiqin Xu , Chen Xu , Yun Liu , Zhaojuan Yang , Lvzhu Xiang , You Zuo , Ningqian Zheng , Zhiqian Ye , Wangjie Xu , Yingbin Liu , Yongzhong Liu , Li Zhang","doi":"10.1016/j.canlet.2025.217786","DOIUrl":"10.1016/j.canlet.2025.217786","url":null,"abstract":"<div><div>Intrahepatic cholangiocarcinoma (iCCA) possesses the immunosuppressive tumor microenvironment (TME) that limits the effectiveness of immunotherapy. Genetic alterations of the coat protein complex Ⅰ (COPⅠ) lead to STING activation and inflammatory immune response. This study aims to address whether targeting COPⅠ can be exploited as a strategy to elicit immune response and inhibit iCCA progression. Here, we demonstrated that the COPⅠ subunits were highly expressed in human and mouse iCCA tissues. Genetic and pharmacological inhibition of COPⅠ suppressed growth of the mouse autochthonous iCCAs driven by activated oncogenes. Disruption of COPⅠ increased T cell presence in tumor environment and elicited anti-tumor T cell response through activating STING-type‐I interferon (IFN‐I) pathway. Neutralizing CD8<sup>+</sup> T cell or STING deletion efficiently counteracted the suppression of iCCA growth by targeting COPⅠ. In addition, the Wnt/β-catenin signaling was dramatically attenuated in tumor cells by STING activation in the context of COPⅠ disruption. Notably, targeting COPⅠ markedly potentiates the therapeutic efficacy of anti-PD-1 in suppressing iCCA growth. In conclusion, our study reveals that targeting COPⅠ effectively suppresses tumor growth by enhancing T cell presence and function in mouse iCCA. STING activation by COPⅠ inhibition dedicates the T cell control of iCCA growth. COPⅠ is a potential target for iCCA treatment.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"626 ","pages":"Article 217786"},"PeriodicalIF":9.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942906","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