Cancer letters最新文献_第2页

Inhibition of DDX3 modulates immune signaling in aggressive breast cancers 抑制DDX3调节侵袭性乳腺癌的免疫信号。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-26 DOI: 10.1016/j.canlet.2025.218065

Farhad Vesuna , Paul T. Winnard Jr. , Marise Heerma van Voss , Guus M. Bol , Natalie D. ter Hoeve , Paul J. van Diest , Venu Raman

{"title":"Inhibition of DDX3 modulates immune signaling in aggressive breast cancers","authors":"Farhad Vesuna , Paul T. Winnard Jr. , Marise Heerma van Voss , Guus M. Bol , Natalie D. ter Hoeve , Paul J. van Diest , Venu Raman","doi":"10.1016/j.canlet.2025.218065","DOIUrl":"10.1016/j.canlet.2025.218065","url":null,"abstract":"<div><div>Triple-negative breast cancers (TNBCs) and inflammatory breast cancer (IBC) are by far the most deadly among all breast cancer subtypes mainly due to being resistant to current treatments. Existing therapies for TNBC and IBC are inadequate due to a limited number of targetable biomarkers and the heterogeneous nature of this disease. In our ongoing search to identify targetable biomarkers for TNBC and IBC, we have found that a member of the RNA helicase protein family, DDX3, is overexpressed in IBC and can be targeted by a small molecule inhibitor which we rationally synthesized, referred to as RK-33. Preliminary data indicate that RK-33 can efficiently and specifically kill TNBC and IBC cell lines without affecting normal breast cells. In the present study, we demonstrate the effectiveness of targeting DDX3 with RK-33 to induce cell death, decrease mammosphere formation, and alter the self-renewal capacity of IBC cells. Additionally, RK-33 was able to disrupt inflammatory cytokine expression in IBC cells. Furthermore, we show that RK-33 sequesters β-catenin in the cytoplasm and decreases Survivin levels in TNBC cells. Moreover, targeting DDX3 with RK-33 promotes multipolar division, leading to cellular death. Importantly, the use of RK-33 also converts high glycolytic tumors to a low glycolytic state, resulting in decreased lactate levels, inhibiting tumor growth, and activating the immune system in an immunocompetent preclinical model of TNBC. Collectively, our data supports the use of RK-33 as a novel therapeutic option for treating TNBC and IBCs.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"634 ","pages":"Article 218065"},"PeriodicalIF":10.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184686","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

MRC2 expression modulates metabolism in acute myeloid leukemia stem cells. MRC2表达调节急性髓系白血病干细胞的代谢。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-26 DOI: 10.1016/j.canlet.2025.218068

Taylor S Mills, Marlon Arnone, Elsa Görsch, Simone Poeschel, Stefan Winter, Jessica Kuebler, Lucca M Kimmich, Florian A Büttner, Jan Weller, Saskia S Rudat, Lucas Mix, Jan C Schroeder, Anna M Paczulla Stanger, Matthias Schwab, Claudia Lengerke

{"title":"MRC2 expression modulates metabolism in acute myeloid leukemia stem cells.","authors":"Taylor S Mills, Marlon Arnone, Elsa Görsch, Simone Poeschel, Stefan Winter, Jessica Kuebler, Lucca M Kimmich, Florian A Büttner, Jan Weller, Saskia S Rudat, Lucas Mix, Jan C Schroeder, Anna M Paczulla Stanger, Matthias Schwab, Claudia Lengerke","doi":"10.1016/j.canlet.2025.218068","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.218068","url":null,"abstract":"<p><p>Leukemic stem cells (LSC) are well recognized for their essential roles in acute myeloid leukemia (AML) initiation and relapse. LSC can be distinguished from non-LSC AML cells by the expression of specific cell surface markers, but there is considerable phenotypic heterogeneity among LSC in AML. Here, using primary patient samples, we report that mannose receptor C-type 2 (MRC2) can be used to enrich for LSC across various AML subtypes. When compared to MRC2- AML cells isolated from the same patient samples, MRC2+ leukemic subpopulations show increased in vitro clonogenic capacity, a stemness transcriptomic signature, and enhanced leukemic capacity in mouse xenograft models. Further, we find that MRC2 is functional on AML cells, and enables their robust uptake of collagen, which supports their glycolytic metabolism. In sum these data highlight the use of functional surface markers to distinguish LSC in AML, and how they can yield insight into their unique characteristics.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218068"},"PeriodicalIF":10.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184646","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

Exploiting metabolic vulnerabilities in cancer: From mechanisms to therapeutic opportunities 利用癌症中的代谢脆弱性：从机制到治疗机会。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-26 DOI: 10.1016/j.canlet.2025.218067

Zeng-Rong Xue, Yuan-Yuan Xin, Wei-Lin Jin

{"title":"Exploiting metabolic vulnerabilities in cancer: From mechanisms to therapeutic opportunities","authors":"Zeng-Rong Xue, Yuan-Yuan Xin, Wei-Lin Jin","doi":"10.1016/j.canlet.2025.218067","DOIUrl":"10.1016/j.canlet.2025.218067","url":null,"abstract":"<div><div>Metabolic reprogramming enables cancer cells to adapt to hostile microenvironments and resist therapy, while simultaneously revealing metabolic vulnerabilities that offer new opportunities for targeted treatment. This review is the first to propose a unified ‘Mechanism–Strategy–Translation’ framework, focusing on two core mechanisms underlying metabolic vulnerability: metabolic inflexibility and synthetic lethality. This dual-axis model not only elucidates how metabolic reprogramming drives tumor progression but also highlights the \"Achilles' heel\" of malignant tumors. The article provides an in-depth discussion of key metabolic pathways on which tumors depend (such as glucose metabolism), epigenetic regulation (e.g., lactylation), and multi-layered stress defense mechanisms—including autophagy, redox homeostasis, anti-ferroptosis, and cuproptosis—while dissecting their inherent vulnerabilities. Furthermore, it emphasizes the tripartite crosstalk among neural, immune, and metabolic components within the TME, systematically explaining how neural signals, immunometabolic reprogramming, and key metabolites collectively regulate tumorigenesis, along with a commentary on the role of microbiota in the TME. Based on these mechanisms, we summarize several emerging targets with clinical translational potential, providing clear directions for future research. Strategies such as combination therapies and dietary interventions are also considered highly promising. Despite ongoing challenges such as metabolic heterogeneity, the deepening integration of multidisciplinary approaches and advances in AI-driven multi-omics analyses are paving the way for transformative prospects in cancer therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"634 ","pages":"Article 218067"},"PeriodicalIF":10.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184637","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

Tumor-derived CCL5 recruits CCR1⁺ macrophages to suppress apoptosis and drive proliferation in duodenal adenocarcinoma. 肿瘤源性CCL5招募CCR1+巨噬细胞抑制十二指肠腺癌细胞凋亡并驱动增殖。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-25 DOI: 10.1016/j.canlet.2025.218064

Jiaoduan Li, Liyi Zhang, Chen Zheng, Xiaolin Lin, Dongyan Cao, Shasha Zhao, Shuang Wang, Bin Yu, Guiying Wei, Xianming Kong, Xiao Liu, Aina He, Xiuying Xiao, Dongxi Xiang

{"title":"Tumor-derived CCL5 recruits CCR1<sup>+</sup> macrophages to suppress apoptosis and drive proliferation in duodenal adenocarcinoma.","authors":"Jiaoduan Li, Liyi Zhang, Chen Zheng, Xiaolin Lin, Dongyan Cao, Shasha Zhao, Shuang Wang, Bin Yu, Guiying Wei, Xianming Kong, Xiao Liu, Aina He, Xiuying Xiao, Dongxi Xiang","doi":"10.1016/j.canlet.2025.218064","DOIUrl":"10.1016/j.canlet.2025.218064","url":null,"abstract":"<p><p>Duodenal adenocarcinoma (DA) is a rare gastrointestinal malignancy associated with poor prognosis and limited therapeutic options. To define the DA tumor microenvironment (TME), we performed single-cell RNA sequencing (scRNA-seq) on primary DA tumors and matched adjacent normal tissues. This analysis revealed substantial heterogeneity among malignant epithelial cells, including a transcriptionally distinct subset characterized by the upregulation of immune-related genes, which constitutes an immune-associated transcriptional program. Notably, this program included high expression of the chemokine CCL5, which facilitated the recruitment of CCR1<sup>+</sup> macrophages. Using patient-derived DA organoids, we identified malignant cells exhibiting immune-related transcriptional signatures, including elevated CCL5. Functional assays demonstrated that CCL5 promoted CCR1<sup>+</sup> macrophage migration, an effect suppressed by both the CCR1 antagonist BX471 and CCL5-neutralizing antibody. In co-culture, CCL5-expressing DA organoids displayed enhanced survival and proliferation in the presence of CCR1<sup>+</sup> macrophages, while pharmacological blockade of CCR1 significantly increased tumor cell death. Bulk transcriptomic profiling revealed that CCR1 downregulates pro-apoptotic signaling in tumor cells, thereby promoting cell survival and growth. Importantly, combining CCL5/CCR1 inhibitors with standard chemotherapeutic agents resulted in synergistic tumor cell killing. Together, our findings establish the CCL5/CCR1 axis as a key mediator of tumor-macrophage crosstalk in DA, supporting immune evasion and chemoresistance via suppression of macrophage-induced apoptosis. Targeting this axis may represent a promising therapeutic strategy to enhance the efficacy of conventional chemotherapy in DA.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218064"},"PeriodicalIF":10.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181860","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

Oncoprotein SND1-enriched exosomes facilitate melanoma lung metastasis by regulating CD47-SIRPα-mediated macrophage reprogramming 癌蛋白snd1富集外泌体通过调节cd47 - sirp α介导的巨噬细胞重编程促进黑色素瘤肺转移。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-25 DOI: 10.1016/j.canlet.2025.218037

Yuankun Chen , Xinting Wang , Hongshuai Li , Zihan Zhang , Yixiang Gao , Lin Ge , Lingbiao Xin , Xingjie Gao , Lei Shi , Jihui Hao , Zhi Yao , Jun Chen , Xi Yang , Jie Yang

{"title":"Oncoprotein SND1-enriched exosomes facilitate melanoma lung metastasis by regulating CD47-SIRPα-mediated macrophage reprogramming","authors":"Yuankun Chen , Xinting Wang , Hongshuai Li , Zihan Zhang , Yixiang Gao , Lin Ge , Lingbiao Xin , Xingjie Gao , Lei Shi , Jihui Hao , Zhi Yao , Jun Chen , Xi Yang , Jie Yang","doi":"10.1016/j.canlet.2025.218037","DOIUrl":"10.1016/j.canlet.2025.218037","url":null,"abstract":"<div><div>Staphylococcal nuclease and Tudor domain containing 1 (SND1) is an emerging oncoprotein highly expressed in various tumors. Database analyses indicate that SND1 is enriched in tumor-derived exosomes, suggesting its potential role in modulating the tumor microenvironment (TME) via exosomes. Here, we demonstrated that SND1 served as a novel tumor-derived exosome (TEX) marker, influencing macrophage polarization by enriching exosomal membrane proteins. In mice, SND1 enriched in melanoma-derived exosomes promoted lung metastasis, accompanied by increased tumor-associated macrophage (TAM) infiltration. Conversely, SND1-deficient exosomes (Exo<sup>SND1−KO</sup>) shifted macrophage polarization toward an M1 phenotype, creating an anti-tumor immune microenvironment and inhibiting melanoma lung metastasis. Mechanistically, SND1 promoted ESCRT-dependent CD47 sorting, thereby facilitating its incorporation into melanoma-derived exosomes and allowing them to evade macrophage-mediated phagocytosis through the CD47–SIRPα axis. Consequently, macrophages failed to engulf TEXs or tumor cells. Notably, Exo<sup>SND1−KO</sup>, lacking CD47, were preferentially phagocytosed by macrophages, triggering M1 reprogramming via exosome-derived dsDNA activation of the cGAS-STING/TBK1/NF-κB pathway. This process led to increased secretion of inflammatory cytokines (IL-1β, IL-6, TNF-α) and activation of type I cell-mediated immunity. Our study suggests that targeting SND1 enrichment in tumor cells could be a promising strategy to inhibit tumor metastasis.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"634 ","pages":"Article 218037"},"PeriodicalIF":10.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181791","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

Cancer-associated fibroblast secreted DKK1 promotes the immunosuppressive tumor microenvironment and colorectal cancer resistance to chemotherapy 肿瘤相关成纤维细胞分泌的DKK1促进免疫抑制肿瘤微环境和结直肠癌化疗耐药

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-24 DOI: 10.1016/j.canlet.2025.218060

Zhijie Yin , Yuning Zhou , Xudong Zhu , Ryan A. Goettl , Chi Wang , Heidi L. Weiss , B. Mark Evers , Qingding Wang

{"title":"Cancer-associated fibroblast secreted DKK1 promotes the immunosuppressive tumor microenvironment and colorectal cancer resistance to chemotherapy","authors":"Zhijie Yin , Yuning Zhou , Xudong Zhu , Ryan A. Goettl , Chi Wang , Heidi L. Weiss , B. Mark Evers , Qingding Wang","doi":"10.1016/j.canlet.2025.218060","DOIUrl":"10.1016/j.canlet.2025.218060","url":null,"abstract":"<div><div>Chemotherapy is the cornerstone of treatment for colorectal cancer (CRC). However, acquired resistance can lead to a decrease in the efficiency of chemotherapy. Here, we show that cancer-associated fibroblasts (CAFs) play a critical role in acquired resistance to chemotherapy. Treatment with 5-fluorouracil (5-FU), oxaliplatin, or SN38 (an active metabolite of irinotecan) increased DKK1 expression and secretion, activation of MEK/ERK, and upregulation of p53 in CAFs. Knockdown of p53 or inhibition of MEK/ERK blocked the increase in DKK1 expression induced by chemotherapeutic agents in CAFs. Consistently, elevated DKK1 and phospho-ERK levels were found in CAFs isolated from surgically resected samples of patients treated with neoadjuvant therapy compared with non-chemotherapy controls. Treatment with recombinant DKK1 promoted the tumor immunosuppressive functions of CAFs, as noted by the increased expression of immunosuppressive cytokines and chemokines. Administration of 5-FU <em>in vivo</em> increased DKK1 levels in the plasma. Treatment with anti-DKK1 neutralizing antibody blocked 5-FU increased DKK1, repressed myeloid-derived suppressor cell (MDSC) tumor infiltration, increased NK cell tumor infiltration, and concurrently enhanced the antitumor efficacy of 5-FU. The current study identified CAF-secreted DKK1 as a contributing factor to chemotherapy resistance. Importantly, our findings provide evidence for targeting DKK1 to counteract chemotherapy resistance in CRC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"634 ","pages":"Article 218060"},"PeriodicalIF":10.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156804","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

An anti-PD-1 antibody (SCT-I10A) plus anti-EGFR antibody (SCT200) and chemotherapy for RAS/BRAF wild-type metastatic colorectal cancer: A phase Ib study. 抗pd -1抗体(SCT-I10A) +抗egfr抗体（SCT200）和化疗治疗RAS/BRAF野生型转移性结直肠癌：一项Ib期研究

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-24 DOI: 10.1016/j.canlet.2025.218061

Ming Bai, Ning Li, Xianli Yin, Chenghui Huang, Wei Li, Jianwei Yang, Shegan Gao, Xinjun Liang, Chunmei Shi, Jinsheng Wu, Zhenning Wang, Ting Deng, Yi Ba

{"title":"An anti-PD-1 antibody (SCT-I10A) plus anti-EGFR antibody (SCT200) and chemotherapy for RAS/BRAF wild-type metastatic colorectal cancer: A phase Ib study.","authors":"Ming Bai, Ning Li, Xianli Yin, Chenghui Huang, Wei Li, Jianwei Yang, Shegan Gao, Xinjun Liang, Chunmei Shi, Jinsheng Wu, Zhenning Wang, Ting Deng, Yi Ba","doi":"10.1016/j.canlet.2025.218061","DOIUrl":"10.1016/j.canlet.2025.218061","url":null,"abstract":"<p><p>Immunotherapy has demonstrated limited efficacy against microsatellite-stable (MSS) metastatic colorectal cancer (mCRC). However, combining epidermal growth factor receptor (EGFR) antibodies with chemotherapy might improve antitumour immune activity. This research evaluated the safety and effectiveness of SCT200 (an anti-EGFR antibody) plus SCT-I10A (an anti-PD-1 inhibitor) with different chemotherapies as first-/second-line therapies for MSS and RAS/BRAF wild-type (WT) mCRC. This open-label, multicentre, phase Ib study tested combination therapies with SCT-I10A, SCT200, and XELOX or IRI regimens in MSS and RAS/BRAF WT mCRC patients. The objective response rate (ORR) and safety were considered primary endpoints. Progression-free survival (PFS), overall survival (OS) and the disease control rate (DCR) served as secondary endpoints of this study. By May 2024, 76 patients were enrolled. Cohort A (first-line) achieved the following: ORR: 78.57 %; DCR: 100 %; mPFS: 12.45 months; and mOS: 25.03 months. Cohort A (second-line) achieved the following: ORR: 63.64 %; DCR: 90.91 %; mPFS: 9.28 months; and mOS: 20.40 months. Cohort B achieved the following: ORR: 37.5 %; DCR: 87.5 %; mPFS: 6.96 months; and mOS: 20.5 months. Additionally, Olink technology was used to analyze the peripheral immune proteome, and the results demonstrated a significant correlation between efficacy and the activation of immune factors. This trial demonstrated the antitumour activity and acceptable safety of combination therapy in MSS and RAS/BRAF WT mCRC. Oxaliplatin may induce greater immune activation, with GZMA and CXCL13 serving as potential prognostic biomarkers. Thus, combining immunotherapy, EGFR inhibitors, and XELOX represents an optimal therapeutic strategy for mCRC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"218061"},"PeriodicalIF":10.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173860","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

RAD21-mediated epigenetic regulation promotes lung adenocarcinoma progression and sensitizes cancer cells to ERK-targeted therapy rad21介导的表观遗传调控促进肺腺癌的进展，并使癌细胞对erk靶向治疗敏感。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-24 DOI: 10.1016/j.canlet.2025.218062

Chu Xiao , Tao Fan , Di Wang , Hongfei Yin , Ziqin Deng , Wenpeng Cai , Yu Ji , Yixiao Liu , Jia Li , Tianle Liao , Chunxiang Li , Jie He

{"title":"RAD21-mediated epigenetic regulation promotes lung adenocarcinoma progression and sensitizes cancer cells to ERK-targeted therapy","authors":"Chu Xiao , Tao Fan , Di Wang , Hongfei Yin , Ziqin Deng , Wenpeng Cai , Yu Ji , Yixiao Liu , Jia Li , Tianle Liao , Chunxiang Li , Jie He","doi":"10.1016/j.canlet.2025.218062","DOIUrl":"10.1016/j.canlet.2025.218062","url":null,"abstract":"<div><div>The cohesin complex, a critical chromatin organizer and transcriptional regulator, is pivotal in oncogenesis. In lung adenocarcinoma (LUAD), its core subunit <em>RAD21</em> is frequently amplified and overexpressed. However, its functional mechanisms and potential in targeted-therapy improvement remain elusive. Here, survival analysis and immunohistochemistry revealed that high RAD21 protein levels correlate with poor patient prognosis. Genetic depletion of <em>RAD21</em> suppressed LUAD cell proliferation by inducing cell cycle arrest and apoptosis, while significantly reducing metastatic capacity both in vitro and in vivo. Integrated transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analysis demonstrated that RAD21 occupies genomic regions of genes linked to MAPK signaling and metastasis. <em>RAD21</em> depletion repressed epithelial-mesenchymal transition (EMT), focal adhesion, and MAPK/ERK cascade activation. RAD21 further modulated H3K4me3 chromatin modification, inducing widespread transcriptional dysregulation of cancer-associated genes. Pharmacological ERK inhibition with ulixertinib effectively reversed <em>RAD21</em>-driven metastasis, particularly in <em>KRAS</em>-mutant contexts. Our findings establish <em>RAD21</em>-mediated epigenetic regulation as a novel mechanism driving LUAD progression. The efficacy of ulixertinib in suppressing cancer metastasis in preclinical models highlights its translational potential for LUAD therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"634 ","pages":"Article 218062"},"PeriodicalIF":10.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173801","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 "Nanoemulsion formulation of a novel taxoid DHA-SBT-1214 Inhibits prostate cancer stem cell-induced tumor growth" [Cancer Lett. 2017 Aug 11;406:71-80]. “新型类taxoid DHA-SBT-1214抑制前列腺癌干细胞诱导肿瘤生长的纳米乳配方”的更正[癌症杂志，2017年8月11日；406:71-80]。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-23 DOI: 10.1016/j.canlet.2025.218043

Gulzar Ahmad, Rana El Sadda, Galina Botchkina, Iwao Ojima, James Egan, Mansoor Amiji

引用次数: 0

AI-informed computational pathology classifier predicts outcomes across treatment modalities in muscle-invasive urothelial carcinoma 人工智能信息的计算病理学分类器预测肌肉侵袭性尿路上皮癌治疗方式的结果。

IF 10.1 1区医学

Cancer letters Pub Date : 2025-09-23 DOI: 10.1016/j.canlet.2025.218059

Kamal Hammouda , Naoto Tokuyama , Germán Corredor , Tilak Pathak , Rishi Dakarapu , Elizabeth Genega , Omar Y. Mian , Paul G. Pavicic Jr. , C. Marcela Diaz-Montero , Tuomas Mirtti , Xavier Farré , Shilpa Gupta , Anant Madabhushi

{"title":"AI-informed computational pathology classifier predicts outcomes across treatment modalities in muscle-invasive urothelial carcinoma","authors":"Kamal Hammouda , Naoto Tokuyama , Germán Corredor , Tilak Pathak , Rishi Dakarapu , Elizabeth Genega , Omar Y. Mian , Paul G. Pavicic Jr. , C. Marcela Diaz-Montero , Tuomas Mirtti , Xavier Farré , Shilpa Gupta , Anant Madabhushi","doi":"10.1016/j.canlet.2025.218059","DOIUrl":"10.1016/j.canlet.2025.218059","url":null,"abstract":"<div><div>Urothelial carcinoma (UC) is one of the leading causes of cancer-related mortality, and effective, scalable biomarkers for treatment planning remain limited. We present UC-TIL, an artificial intelligence (AI)-based model that quantifies spatial patterns of tumor-infiltrating lymphocytes (TILs) from routine H&E-stained slides to predict survival and immunotherapy response. We analyzed 558 whole-slide images across three cohorts: TCGA (D<sub>0</sub>&<sub>1</sub>, N = 292), Emory (D<sub>2</sub>, N = 161), and TRRC2819 (D<sub>3</sub>, N = 105), spanning chemotherapy and immune checkpoint inhibitor (ICI) treatments. UC-TIL classification was associated with OS (HR = 2.11, 95 %CI:1.01–4.41, p = 0.011) and PFS (HR = 3.68, 95 %CI:1.07–12.65, p = 0.0012) in locally advanced disease (D<sub>1</sub> and D<sub>2</sub>), with consistent results in metastatic disease (D<sub>3</sub>) (HR = 1.73, 95 %CI:1.08–2.77, p = 0.043; PFS HR = 1.73, 95 %CI:1.07–2.81, p = 0.047). In the ICI-treated D<sub>3</sub> cohort, UC-TIL achieved AUC = 0.757 and identified non-responders with 91 % specificity. UC-TIL enables reliable risk stratification and treatment response prediction in both locally advanced and metastatic urothelial carcinoma by analyzing spatial TIL patterns from standard pathology slides. These findings position UC-TIL as a readily deployable tool to guide personalized therapy across multiple clinical settings.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"634 ","pages":"Article 218059"},"PeriodicalIF":10.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147795","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