Cancer letters最新文献_第6页

Antimetastatic activity of B7-H3-targeted CAR T-cell therapy in triple-negative breast cancer b7 - h3靶向CAR -t细胞治疗三阴性乳腺癌的抗转移活性

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-28 Epub Date: 2026-02-19 DOI: 10.1016/j.canlet.2026.218345

Franziska Hausmann , Tatsuya Kobayashi , Luke Maggs , Max N. Meyer , Shahrzad Arya , Cristina R. Ferrone , Xinhui Wang , Soldano Ferrone , Dan G. Duda

引用次数: 0

Cancer cell metastasis and drug resistance: Unravelling the role of NF-κB and cyclin D1 pathways and their crosstalk 癌细胞转移与耐药：NF-κB和Cyclin D1通路的作用及其串扰。

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-10 Epub Date: 2026-02-09 DOI: 10.1016/j.canlet.2026.218314

Debasish Kumar Dey , Kasturi Ganguly , Enish Kujur , Soumen Basak

{"title":"Cancer cell metastasis and drug resistance: Unravelling the role of NF-κB and cyclin D1 pathways and their crosstalk","authors":"Debasish Kumar Dey , Kasturi Ganguly , Enish Kujur , Soumen Basak","doi":"10.1016/j.canlet.2026.218314","DOIUrl":"10.1016/j.canlet.2026.218314","url":null,"abstract":"<div><div>The emergence of drug resistance in cancer therapy remains a formidable challenge. NF-κB transcription factor is considered a central player in therapeutic resistance and tumor relapse. Upon activation, NF-κB dimers trigger a cascade of downstream signaling and transcriptional events that promote cell proliferation and survival. One of the key NF-κB targets is cyclin D1, which facilitates uncontrolled cell division in both CDK-dependent and independent manners. NF-κB-mediated upregulation of cyclin D1 is associated with drug resistance by activating multiple mechanisms, including anti-apoptotic pathways, epithelial-to-mesenchymal transition, epigenetic modifications, and DNA damage repair. Therefore, a comprehensive understanding of the interplay between NF-κB and cyclin D1 may inform the development of improved therapeutic strategies that simultaneously target multiple resistance pathways and suppress the growth, proliferation, and metastasis of cancer cells. This review focuses on the molecular mechanisms by which the NF-κB and cyclin D1 axis contributes to drug resistance, explores its crosstalk with other oncogenic pathways, and discusses the pivotal roles as a therapeutic target and clinical trials with an agent that targets the NF-κB signaling pathway. By unravelling the intricate dynamics of this axis, we can pave the way for more effective strategies to overcome drug resistance in cancer therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"643 ","pages":"Article 218314"},"PeriodicalIF":10.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164191","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

Letter to the editor on “Dietary intake of the red meat-derived glycan Neu5Gc fuels colorectal cancer through up-regulation of Wnt signaling pathway” 致编辑关于“膳食摄入红肉衍生聚糖Neu5Gc通过上调Wnt信号通路促进结直肠癌”的信。

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-10 Epub Date: 2026-02-09 DOI: 10.1016/j.canlet.2026.218317

M.C. Muollo , L. Biagini , D. De Bellis , F. Carnevali , G. Rossi

引用次数: 0

Targeting Galectin-9 to overcome immunosuppression and potentiate ATR inhibitor therapy 靶向半乳糖凝集素-9克服免疫抑制和增强ATR抑制剂治疗。

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-10 Epub Date: 2026-02-04 DOI: 10.1016/j.canlet.2026.218283

Delong Liu , Boning Liu , Riyao Yang , Jiaming Song , Qihui Chen , Zhiguo Liu , Shunjie Xiong , Shasha Shi , Mien-Chie Hung , Linlin Sun

{"title":"Targeting Galectin-9 to overcome immunosuppression and potentiate ATR inhibitor therapy","authors":"Delong Liu , Boning Liu , Riyao Yang , Jiaming Song , Qihui Chen , Zhiguo Liu , Shunjie Xiong , Shasha Shi , Mien-Chie Hung , Linlin Sun","doi":"10.1016/j.canlet.2026.218283","DOIUrl":"10.1016/j.canlet.2026.218283","url":null,"abstract":"<div><div>Pharmacological targeting of ATR (ataxia telangiectasia and Rad3-related kinase), the master regulator of replication stress response, is emerging as a promising anticancer strategy. Despite the documented immune-modulatory effects of ATR inhibitors (ATRi), the immune evasion mechanisms constraining their therapeutic efficacy remain undefined. Here, we demonstrate that ATRi upregulates Galectin-9 (Gal-9), a ligand for the TIM-3 immune checkpoint, in tumor cells and host antigen-presenting cells (dendritic cells/macrophages) via STING-type I interferon (IFN-I) innate immune pathway. Notably, combining Gal-9 blockade with ATRi ceralasertib elicits potent anti-tumor effects and induces durable immunologic memory in syngeneic mouse models. In immune checkpoint-refractory lung cancer, the triple combination of ATRi, anti-Gal-9 and anti-PD-1 demonstrates superior efficacy. Mechanistically, Gal-9 blockade synergizes with ATRi to activate dendritic cells/macrophages and promote CD8<sup>+</sup> T cell differentiation toward stem-like memory phenotypes with enhanced functional capacity. CD8<sup>+</sup> T cell depletion completely abrogates the anti-tumor effects, suggesting their essential role in mediating therapeutic responses. These findings establish Gal-9 upregulation as a critical adaptive immune resistance mechanism constraining ATRi efficacy, providing a compelling rationale for clinical translation of ceralasertib/anti-Gal-9 combinations.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"643 ","pages":"Article 218283"},"PeriodicalIF":10.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131045","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

ZBTB20 promotes malignancy and stemness in lung squamous cell carcinoma through the transcriptional repression of KCTD1 and activation of Hedgehog signaling ZBTB20通过抑制KCTD1转录和激活Hedgehog信号通路促进肺鳞状细胞癌的恶性和干性。

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-10 Epub Date: 2026-02-09 DOI: 10.1016/j.canlet.2026.218301

Hai Wang , Xueqi Tian , Wanli Zhu , Yichao Wang , Yong Yang

{"title":"ZBTB20 promotes malignancy and stemness in lung squamous cell carcinoma through the transcriptional repression of KCTD1 and activation of Hedgehog signaling","authors":"Hai Wang , Xueqi Tian , Wanli Zhu , Yichao Wang , Yong Yang","doi":"10.1016/j.canlet.2026.218301","DOIUrl":"10.1016/j.canlet.2026.218301","url":null,"abstract":"<div><div>Prostate Potassium channel tetramerization domain containing 1 (KCTD1) is a tumor suppressor that inhibits the Hedgehog (Hh) signaling pathway. The aim of this study was to investigate the role of KCTD1 in lung squamous cell carcinoma (LUSC) and its impact on the Hedgehog (Hh) pathway. Jervine, a known Hh signaling inhibitor, was used to validate the function KCDT1. After ascertaining the expression pattern of KCTD1 in LUSC tissues, gain- and loss-of-function experiments were conducted to analyze the impact of KCTD1 on the malignant behavior and stemness of LUSC cells malignancy, and the activation of Hh pathway. Tumor allografts were established in mice for <em>in vivo</em> validation. Zinc finger and BTB domain-containing 20 (ZBTB20) was identified as a potential upstream regulator of KCDT1 through bioinformatics approaches. To determine the role of ZBTB20 in LUSC progression, the cell lines were transfected with the expression construct, and Jervine was used for functional rescue experiments. Although KCTD1 was upregulated in LUSC, its expression predicted a favorable prognosis. KCTD1 knockdown reduced the proliferation, migration, clonogenic potential, and stemness of LUSC cells by activating the Hh pathway, while Jervine treatment reversed these oncogenic effects. Furthermore, ZBTB20 was downregulated in the LUSC tissues, and its overexpression downregulated KCTD1 through transcriptional repression, and activated the Hh pathway, thereby enhancing the malignant behavior of LUSC cells. However, these oncogenic effects were counteracted by either Jervine treatment, or by restoring KCTD1 expression. Overall, this study shows that KCTD1 reduces malignancy and stemness in LUSC cells by inactivating the Hh signaling pathway.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"643 ","pages":"Article 218301"},"PeriodicalIF":10.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163985","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

Bidirectional relationship between cancer and depression: From shared mechanisms to integrated therapeutic strategies 癌症与抑郁的双向关系：从共同机制到综合治疗策略。

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-10 Epub Date: 2026-02-09 DOI: 10.1016/j.canlet.2026.218318

Zichen Liu , Jiaming Wan , Shupeng Liu

{"title":"Bidirectional relationship between cancer and depression: From shared mechanisms to integrated therapeutic strategies","authors":"Zichen Liu , Jiaming Wan , Shupeng Liu","doi":"10.1016/j.canlet.2026.218318","DOIUrl":"10.1016/j.canlet.2026.218318","url":null,"abstract":"<div><div>Cancer and depression exhibit a clinically significant bidirectional association, as evidenced by the key findings: cancer patients are prone to depression, and depressed patients are prone to cancer. This may help explain why depression is commonly observed in cancer populations, where it is associated with poorer treatment adherence, diminished quality of life, and elevated mortality. Conversely, depression associated with an elevated cancer risk, potentially mediated by factors, such as neuroimmune dysregulation, chronic inflammation, and unhealthy lifestyles. Shared mechanisms include stress-induced β-adrenergic signaling, neuroinflammation, kynurenine pathway activation, and gut-brain-tumor axis disruptions involving bacterial metabolites like acetate. Common lifestyle factors such as smoking and sleep disruption, may further link both conditions through pathways like Wnt/β-catenin and JAK/STAT. Integrated treatment strategies combining anti-inflammatory medications such as non-steroidal anti-inflammatory drugs (NSAIDs) or tumor necrosis factor-α (TNF-α) inhibitors, psychotropic medications such as selective serotonin reuptake inhibitors (SSRIs), lifestyle modifications (e.g., exercise, Mediterranean diet) and psychotherapy (e.g., CBT) are promising for breaking the potential depression-cancer cycle and improving outcomes.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"643 ","pages":"Article 218318"},"PeriodicalIF":10.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164230","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

LINC01978 drives perineural invasion in cholangiocarcinoma through tumor-neural crosstalk and CCL2-mediated macrophage recruitment LINC01978通过肿瘤-神经串扰和ccl2介导的巨噬细胞募集驱动胆管癌的神经周围侵袭。

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-10 Epub Date: 2026-02-06 DOI: 10.1016/j.canlet.2026.218304

Haoran Li , Runhe Zhou , Xueling Wang , Zhaowei Sun , Kai Ma , Bingyuan Zhang , Qinlei Wang , Chuan Feng , Bin Zhou , Yujie Feng

{"title":"LINC01978 drives perineural invasion in cholangiocarcinoma through tumor-neural crosstalk and CCL2-mediated macrophage recruitment","authors":"Haoran Li , Runhe Zhou , Xueling Wang , Zhaowei Sun , Kai Ma , Bingyuan Zhang , Qinlei Wang , Chuan Feng , Bin Zhou , Yujie Feng","doi":"10.1016/j.canlet.2026.218304","DOIUrl":"10.1016/j.canlet.2026.218304","url":null,"abstract":"<div><div>Perineural invasion (PNI) is a major contributor to the aggressiveness and poor prognosis of cholangiocarcinoma (CCA). However, the crosstalk among tumor cells, the peripheral nervous system, and tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) remains incompletely defined. Using in vitro and in vivo models of PNI, we demonstrate that tumor-derived exosomal LINC01978 mediates neural reprogramming and TAM-associated extracellular matrix (ECM) remodeling. Subsequent analyses of clinical cohorts confirm that high LINC01978 expression is significantly associated with PNI and poorer survival. This mechanism is further validated in human specimens by IHC and IF. Mechanistically, we propose a nerve-coupled dual-loop model that drives PNI in CCA. In the first loop, tumor-derived exosomes deliver LINC01978 to neural cells. This process promotes neurite outgrowth via autocrine glial cell line-derived neurotrophic factor (GDNF) signaling, which in turn activates the RET/STAT3 signaling pathway in CCA cells, thereby promoting malignant phenotypes. After this loop is established, a second loop emerges at the invasive front. Invaded nerves secrete CCL2, thereby preferentially recruiting CCR2+ inflammatory monocytes (IMs) to PNI sites, where they differentiate into TAMs and secrete CTSB to degrade the perineural ECM. Together, the two loops act sequentially and reinforce each other, creating a self-amplifying program that escalates PNI.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"643 ","pages":"Article 218304"},"PeriodicalIF":10.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141126","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 endoplasmic reticulum stress-regulated XBP1s transcription factor drives a negative feedback loop on FLT3 expression in leukemia cells 内质网应激调节的XBP1s转录因子在白血病细胞中驱动FLT3表达的负反馈回路。

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-10 Epub Date: 2026-02-10 DOI: 10.1016/j.canlet.2026.218310

Céline Philippe , Manon Jaud , Clara Da Cunha , Loïc Van Den Berghe , Manon Farce , Marina Bousquet , Stéphane Pyronnet , Laurent Mazzolini , Christian Touriol

引用次数: 0

Liver cancer-derived exosomal PTK6 induces the secretion of pulmonary CHI3L1 to facilitate lung metastatic niche formation 肝癌来源的外泌体PTK6诱导肺CHI3L1的分泌，促进肺转移生态位的形成。

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-10 Epub Date: 2026-02-09 DOI: 10.1016/j.canlet.2026.218312

Jinxian Yang , Han Yu , Caiming Zhong , Lingyan Xu , Yuting Song , Yushan Miao , Qiqi Cao , Wen Wen , Hao Tang , Shuzhen Chen , Hongyang Wang

{"title":"Liver cancer-derived exosomal PTK6 induces the secretion of pulmonary CHI3L1 to facilitate lung metastatic niche formation","authors":"Jinxian Yang , Han Yu , Caiming Zhong , Lingyan Xu , Yuting Song , Yushan Miao , Qiqi Cao , Wen Wen , Hao Tang , Shuzhen Chen , Hongyang Wang","doi":"10.1016/j.canlet.2026.218312","DOIUrl":"10.1016/j.canlet.2026.218312","url":null,"abstract":"<div><div>Pulmonary metastasis represents the most frequent site of distant dissemination in hepatocellular carcinoma (HCC). Elevated levels of Chitinase-3-like protein 1 (CHI3L1) in HCC patients are specifically associated with pulmonary metastasis, compared to metastasis to other sites or the absence of metastasis. HCC-derived exosomes, enriched in protein tyrosine kinase 6 (PTK6), induced CHI3L1 secretion in pulmonary epithelial cells via PTK6-mediated STAT3 phosphorylation (p-STAT3), thereby promoting angiogenesis and facilitating the establishment of a lung pre-metastatic niche. Elevated CHI3L1 enhanced HCC cell migration and angiogenesis, facilitating pulmonary metastatic niche formation. Targeting CHI3L1 with neutralizing antibodies or AAV2-shChi3l1 knockdown in pulmonary cells significantly reduced lung metastasis in vivo. Furthermore, Bortezomib suppressed CHI3L1 secretion in vitro and in vivo, inhibiting HCC lung metastasis. This study establishes CHI3L1 as a specific biomarker and a therapeutic target for HCC pulmonary metastasis.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"643 ","pages":"Article 218312"},"PeriodicalIF":10.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164201","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

Cross-species single-cell and spatial transcriptomic mapping reveals EFNA1–EPHA4–mediated stem-like epithelial–macrophage crosstalk driving colorectal cancer progression 跨物种单细胞和空间转录组图谱揭示了efna1 - epha4介导的干细胞样上皮-巨噬细胞串扰驱动结直肠癌的进展

IF 10.1 1区医学

Cancer letters Pub Date : 2026-04-09 DOI: 10.1016/j.canlet.2026.218495

Siwen Zhang , Kun Xu , Yanyun Du , Zhenhao Liu , Hong Li , Bing Li , Lu Xie , Yunshi Zhong

{"title":"Cross-species single-cell and spatial transcriptomic mapping reveals EFNA1–EPHA4–mediated stem-like epithelial–macrophage crosstalk driving colorectal cancer progression","authors":"Siwen Zhang , Kun Xu , Yanyun Du , Zhenhao Liu , Hong Li , Bing Li , Lu Xie , Yunshi Zhong","doi":"10.1016/j.canlet.2026.218495","DOIUrl":"10.1016/j.canlet.2026.218495","url":null,"abstract":"<div><div>Colorectal cancer (CRC) typically follows the \"normal–adenoma–carcinoma\" (NAC) progression, with approximately 70–90% of cases driven by an adenomatous polyposis coli (APC) mutation-dependent pathway. The Apc-mutant (Min) mouse, valuable for dissecting gene function and mechanisms in CRC, provides an important basis for cross-species analyses with human data. Here, we performed a cross-species analysis of single-cell and spatial transcriptomic data across multiple stages of colorectal tissues in both humans and Min mice, constructing a spatiotemporal atlas. Our study identified key microenvironmental regulatory networks involved in CRC progression and highlighted the central role of epithelial–macrophage interactions within the tumor microenvironment. We further validated the suitability of the Min mouse as a model for the intrinsic Consensus Molecular Subtypes 2(iCMS2) microsatellite-stable (MSS) subtype of CRC. Focusing on the crosstalk between tumor-associated macrophages (TAMs) and epithelial cells, we identified the EFNA1–EPHA4 axis as a critical regulator promoting the immunosuppressive polarization of TAMs and enhancing tumor cell stemness. In addition, inhibition of EFNA1 was found to slow tumor growth. This study not only provides a systematic framework for mapping CRC correspondence between humans and mice, but also uncovers key molecular mechanisms underlying CRC progression and proposes promising therapeutic targets.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"649 ","pages":"Article 218495"},"PeriodicalIF":10.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147661440","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