Cancer Science最新文献

{"title":"How Do Cancer Cells Create Cancer-Associated Fibroblast Subtypes? Impacts of Extracellular Vesicles on Stromal Diversity","authors":"Yutaka Naito","doi":"10.1111/cas.70133","DOIUrl":"10.1111/cas.70133","url":null,"abstract":"<p>Cancer-associated fibroblasts (CAFs) are the major component of the tumor stroma. They mediate various attributes of tumor cells, such as cell growth, migration, invasion, angiogenesis, metabolic reprogramming, apoptosis, immune regulation, and extracellular matrix reconstitution, all related to cancer progression and treatment resistance. Although many researchers have recognized CAF heterogeneity, recent technological advances have emphasized the functional and phenotypic diversity of CAFs in cancer progression. Why are these CAF subtypes generated within tumor tissues? And how do cancer cells dictate such heterogeneous subtypes of CAFs? This review will highlight the CAF subtypes within the tumor microenvironment and their role in tumor progression. CAF subtype induction by extracellular vesicles (EVs) and their significance, which we reported previously, is also discussed.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2347-2361"},"PeriodicalIF":4.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Tumor Necrosis Factor-α Promotes the Lymphangiogenesis of Gallbladder Carcinoma Through Nuclear Factor-κB-Mediated Upregulation of Vascular Endothelial Growth Factor-C”","authors":"","doi":"10.1111/cas.70127","DOIUrl":"10.1111/cas.70127","url":null,"abstract":"<p>Qiang Du, Lei Jiang, Xiaoqian Wang, Meiping Wang, Feifei She, Yanling Chen. Tumor Necrosis Factor-α Promotes the Lymphangiogenesis of Gallbladder Carcinoma Through Nuclear Factor-κB-Mediated Upregulation of Vascular Endothelial Growth Factor-C. Cancer Science 105 (2014) 1261–1271. https://doi.org/10.1111/cas.12504.</p><p>We apologize for this error.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PBK Expression Promotes the Aggressive Phenotypes of Mesothelioma","authors":"Kazumi Hori,&nbsp;Ichidai Tanaka,&nbsp;Tatsuhiro Sato,&nbsp;Mika Sato,&nbsp;Yuta Kodama,&nbsp;Hideyuki Itoigawa,&nbsp;Yuichi Abe,&nbsp;Taketo Kato,&nbsp;Ayumu Taguchi,&nbsp;Mitsuo Sato,&nbsp;Yoshitaka Sekido,&nbsp;Toyofumi Fengshi Chen-Yoshikawa,&nbsp;Makoto Ishii","doi":"10.1111/cas.70124","DOIUrl":"10.1111/cas.70124","url":null,"abstract":"<p>Mesothelioma is one of the most aggressive neoplasms worldwide that has a particularly poor prognosis. We have previously discovered that oxytocin receptors (OXTR) are highly expressed in mesothelioma and that <i>OXTR</i> knockdown significantly decreases the proliferation of mesothelioma cells with high <i>OXTR</i> expression. In this study, we performed quantitative proteomic profiling of two mesothelioma cell lines with high <i>OXTR</i> expression using mass spectrometry to investigate the downstream signals of OXTR in mesothelioma cells. We found that <i>OXTR</i> knockdown significantly downregulated PDZ-binding kinase (PBK)—a serine/threonine protein kinase belonging to the bispecific MAPKK family. <i>PBK</i> knockdown significantly suppressed proliferation, migration, and colony formation in mesothelioma cells with high <i>PBK</i> expression and decreased Akt and MAPK phosphorylation levels. Furthermore, immunohistochemical analysis of PBK in surgical specimens obtained from patients with mesothelioma showed that high PBK expression was strongly associated with poor overall survival (log-rank test <i>p</i> = 0.0031; hazard ratio 3.339 and 95% confidence interval 1.12–10.00) and recurrence-free survival (log-rank test <i>p</i> = 0.0024; hazard ratio 3.355 and 95% confidence interval 1.25–9.04). In addition, the clinical significance of PBK expression was validated in mesothelioma using datasets from TCGA. Multivariable Cox regression analysis, incorporating stage and <i>OXTR</i> mRNA expression, demonstrated that <i>PBK</i> mRNA expression was the strongest independent predictor of OS. Our findings indicate that PBK plays a crucial role in the aggressiveness of mesothelioma, making it a promising therapeutic target and potential prognostic biomarker for mesothelioma.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2413-2426"},"PeriodicalIF":4.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “lncRNA XLOC013218 Promotes Cell Proliferation and TMZ Resistance by Targeting the PIK3R2-Mediated PI3K/AKT Pathway in Glioma”","authors":"","doi":"10.1111/cas.70131","DOIUrl":"10.1111/cas.70131","url":null,"abstract":"<p>Zhou J, Xu N, Liu B, et al. lncRNA XLOC013218 promotes cell proliferation and TMZ resistance by targeting the PIK3R2-mediated PI3K/AKT pathway in glioma. <i>Cancer Sci</i>. 2022; 113:2681–2692. doi:10.1111/cas.15387</p><p>In “3 | RESULTS” section, the text “3.4 | PIK3R2 knockdown reverses the enhanced TMZ sensitivity and promotes the cell survivability effect of XLOC” was incorrect.</p><p>This should have read: “3.4 | PIK3R2 knockdown partly reverses XLOC-mediated TMZ resistance in GBM cells”.</p><p>In “3.4 | PIK3R2 knockdown reverses the enhanced TMZ sensitivity and promotes the cell survivability effect of XLOC” section, the text “To further explore whether PIK3R2 is involved in the effect of XLOC or not, sh-PIK3R2 were transfected into cells stably overexpressing XLOC (U87 and U251 V-XLOC) (Figure 4A). Knockdown of PIK3R2 significantly decreased the sensitivity of GBM cells to TMZ with lower IC50 values (Figure 4B) and suppressed cell viability with TMZ (50μg/ml) treatment when compared with the control groups (Figure 4C, D).” was incorrect.</p><p>This should have read: “To further explore whether PIK3R2 is involved in the effect of XLOC, sh-PIK3R2 was transfected into cells stably overexpressing XLOC (U87 and U251 V-XLOC) (Figure 4A). Knockdown of PIK3R2 significantly increased the sensitivity of GBM cells to TMZ, as indicated by lower IC50 values (Figure 4B), and reduced cell viability upon TMZ (50μg/ml) treatment compared to the control groups (Figure 4C, D).”</p><p>In “3.7 | XLOC as a candidate therapeutic target” section, the text “Immunohistochemistry analysis revealed that PIK3R2 and Ki67 expression was weakly detected, whereas increased C-Cas3 expression was observed in XLOC-overexpressed tumor tissues.” was incorrect.</p><p>This should have read: “Immunohistochemistry analysis revealed that PIK3R2 and Ki67 expression was increased, whereas C-Cas3 expression was suppressed in XLOC-overexpressed tumor tissues.”</p><p>In “3.3 | PIK3R2 is the potential target of XLOC” section, the text “To determine the subcellular localization of XLOC, RNA in situ hybridization (RNA-ISH) was conducted” is incorrect.</p><p>This should have read: “FISH was conducted to determine the subcellular localization of XLOC”.</p><p>In “Figure 1” caption, the text “*<i>p</i> &lt; 0.05, **<i>p</i> &lt; 0.01, ***<i>p</i> &lt; 0.001” is incorrect.</p><p>This should have read: “*<i>p</i> &lt; 0.05, ***<i>p</i> &lt; 0.001”.</p><p>We apologize for these errors.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2618-2619"},"PeriodicalIF":4.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basal Invasion of Cancer Cells Driven by Cell–Cell Interactions: An Affirmative Role of Cell Competition in Cancer Progression","authors":"Kazuki Nakai,&nbsp;Eilma Akter,&nbsp;Shunsuke Kon","doi":"10.1111/cas.70120","DOIUrl":"10.1111/cas.70120","url":null,"abstract":"<p>Cancer develops through the transformation of normal epithelial cells, followed by the expansion of hyperplastic cells within epithelial tissues and the subsequent generation of invasive cells capable of breaching the basement membrane. Basal delamination represents a pivotal early step that primes transformed cells for invasion and accounts for a large part of the lethality associated with carcinomas. Emerging evidence indicates that, upon the appearance of transformed cells, an intricate interplay between these cells and the surrounding epithelial neighbors acts as a potential driver of cancer cell invasion. Notably, certain transformed cells exploit cell competition for their own benefit to guide basal delamination. In this review, we delineate the physiological roles of cell competition in cancer cell dissemination and discuss the molecular cues underlying heterotypic cell interaction-induced basal extrusion.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2340-2346"},"PeriodicalIF":4.3,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial–Mesenchymal Transition and Genetically Driven Early Tumor Seedings in Extraneural Metastasis of Glioblastoma","authors":"Seisaku Kanayama,&nbsp;Kentaro Watanabe,&nbsp;Minoru Tanaka,&nbsp;Junko Takita,&nbsp;Tomoki Todo","doi":"10.1111/cas.70126","DOIUrl":"10.1111/cas.70126","url":null,"abstract":"<p>Genetic and cell biological analyses of this rare glioblastoma (GBM) case with rapidly progressive pleural metastasis revealed essential roles of epithelial–mesenchymal transition (EMT) and glioma stem-like cells (GSCs) in extraneural metastasis. Contrary to the common prediction, the metastatic lesion shared 73% of mutations and two fusion genes with the primary but not the recurrent tumor, indicating that extraneural metastasis occurs early in GBM progression. Functional assays using primary tumor-derived GSCs confirmed EMT-enhanced migratory behaviors. EMT and genetically driven early tumor seedings are crucial for extraneural GBM metastasis, emphasizing the need for further investigation into EMT pathways and GSC biology.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2607-2612"},"PeriodicalIF":4.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression","authors":"Kosuke Hirose,&nbsp;Takaaki Masuda,&nbsp;Hajime Otsu,&nbsp;Taro Tobo,&nbsp;Kiyotaka Hosoda,&nbsp;Tadashi Abe,&nbsp;Yusuke Nakano,&nbsp;Masahiro Hashimoto,&nbsp;Takanari Tatsumi,&nbsp;Tomohiko Ikehara,&nbsp;Takashi Ofuchi,&nbsp;Shinsaku Itoyama,&nbsp;Yuki Ando,&nbsp;Yasuo Tsuda,&nbsp;Yusuke Yonemura,&nbsp;Keishi Sugimachi,&nbsp;Eiji Oki,&nbsp;Tomoharu Yoshizumi,&nbsp;Koshi Mimori","doi":"10.1111/cas.70119","DOIUrl":"10.1111/cas.70119","url":null,"abstract":"<p>Polarity genes form intracellular protein complexes that establish epithelial cell polarity and homeostasis for various normal cellular functions. Partitioning Defective 6B (PARD6B), a polarity gene, functions as a scaffold node for the Par protein complex. However, its contribution to colon cancer is not well understood. In this study, we showed that PARD6B regulates tumor progression in colorectal cancer (CRC). PARD6B is located on chromosome 20, which is frequently amplified in CRC, and its expression in CRC correlates with DNA copy number amplification, including enhancer regions. Immunohistochemistry and single-cell analyses also showed that PARD6B expression was significantly higher in cancer cells. Furthermore, unlike other polarity gene groups comprising the Par complex, PARD6B mRNA expression was the only independent poor prognostic factor. In vitro and in vivo experiments revealed that PARD6B positively regulates cell proliferation and cell cycle progression. In silico analysis also showed that PARD6B expression positively regulated MYC expression, a pathway believed to be associated. Additional in silico and in vitro analyses supported the hypothesis that PARD6B regulates miR-34c, which directly targets and represses MYC expression. Pan-cancer analysis indicated that PARD6B is highly expressed in gastrointestinal tumors, including CRC, and that high PARD6B mRNA expression is a poor prognostic factor in other cancer types. In summary, highly expressed PARD6B can promote CRC growth by upregulating MYC expression while suppressing miR-34c expression, making PARD6B a potential prognostic biomarker and therapeutic target for CRC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2507-2522"},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selinexor Reduces the Immunosuppression of Macrophages and Synergizes With CD19 CAR-T Cells Against B-Cell Lymphoma","authors":"Wenjing Luo,&nbsp;Jia Xu,&nbsp;Chenggong Li,&nbsp;Lu Tang,&nbsp;Yingying Li,&nbsp;Xindi Wang,&nbsp;Zhuolin Wu,&nbsp;Yinqiang Zhang,&nbsp;Heng Mei,&nbsp;Yu Hu","doi":"10.1111/cas.70123","DOIUrl":"10.1111/cas.70123","url":null,"abstract":"<p>CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved high response rates in patients with B-cell lymphoma. However, treatment failure and relapse can be attributable to CAR-T cell dysfunction and the immunosuppression of the tumor microenvironment. Combination therapy emerges as a solution strategy, and selinexor might be a potential candidate. In this study, we first established the ex vivo tumor microenvironment model by coculturing tumor cells and macrophages, followed by coculture with CAR-T cells, and identified that selinexor decreased CAR-T cell exhaustion and enhanced its cytotoxicity. Moreover, selinexor upregulated NGFR expression and boosted CAR-T cell proliferation. The ex vivo and in vivo results showed that selinexor prevented macrophages from polarizing to M2 populations. In the xenograft animal model, the sequential use of selinexor and CAR-T cells significantly reduced the tumor burden compared with selinexor or CAR-T cell monotherapies. In summary, our findings suggest that selinexor mitigates the immunosuppression of macrophages and improves CAR-T cell functionality, and the combination of selinexor and CAR-T cells may be a promising therapeutic strategy for B-cell lymphoma.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2388-2399"},"PeriodicalIF":4.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implication of KLHL Gene Family Member KLHL5 in Colorectal Cancer Progression and Prognosis","authors":"Konomu Uno,&nbsp;Hirotada Nishie,&nbsp;Hiromi Hiyoshi,&nbsp;Kyosuke Habu,&nbsp;Jun Nakayama,&nbsp;Sota Tate,&nbsp;Tomohisa Sakaue,&nbsp;Eiji Kubota,&nbsp;Mamoru Tanaka,&nbsp;Takaya Shimura,&nbsp;Hiromi Kataoka,&nbsp;Takashi Joh,&nbsp;Shigeki Higashiyama","doi":"10.1111/cas.70107","DOIUrl":"10.1111/cas.70107","url":null,"abstract":"<p>The KLHL gene family member KLHL5, which is a constituent factor of the RING E3 ubiquitin ligase complex, is expressed in various types of cancers and plays a role in cancer pathophysiology. In this study, we identified KLHL5 as a potential biomarker for predicting the prognosis of colorectal cancer (CRC) from 42 KLHL family genes using transcriptome profiles generated by RNA-seq analysis of The Cancer Genome Atlas colorectal adenocarcinoma (TCGA-COAD). We further investigated the implication of KLHL5 in CRC using pathological examination and bioinformatics analyses. Clinicopathological analyses revealed that KLHL5 was more highly expressed in CRC than in adjacent normal mucosa, and its expression level increased concomitantly with the CRC stage (<i>p</i> &lt; 0.05). KLHL5 expression was associated with poor prognostic factors such as depth of invasion (<i>p</i> &lt; 0.001), lymphovascular invasion (<i>p</i> = 0.029), and lymph node metastasis (<i>p</i> = 0.025). Notably, KLHL5 exhibited heterogeneous expression within the tumor, with pronounced expression observed at the invasive front of the tumor (<i>p</i> &lt; 0.0001). Through bioinformatics analyses, we determined that elevated KLHL5 expression in CRC is significantly associated with poor prognosis. Furthermore, analysis from the Gene Expression Omnibus database indicated that KLHL5 expression was more pronounced in the common molecular subtype (CMS) 4 CRC, which is characterized as highly advanced, and the overall and recurrence-free survival rates were poor compared to other CMS groups. Our findings indicate that KLHL5 plays a pivotal role in the progression and development of CRC, and can be used as a potential biomarker and therapeutic target for CRC treatment.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2580-2591"},"PeriodicalIF":4.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered EVs-Mediated miR-222 Targeting PTEN/FN1 Axis Reverses Anthracycline Resistance in HER2-Negative Breast Cancer","authors":"Sujin Yang,&nbsp;Mei Yang,&nbsp;Quanfeng Shao,&nbsp;Dandan Wang,&nbsp;Shanliang Zhong,&nbsp;Suyu Yang,&nbsp;Haiyan Gao,&nbsp;Xihu Qin,&nbsp;Weixian Chen","doi":"10.1111/cas.70118","DOIUrl":"10.1111/cas.70118","url":null,"abstract":"<p>Anthracycline resistance represents a critical therapeutic challenge in breast cancer treatment, wherein alterations in the tumor immune microenvironment and enhanced cellular resistance mechanisms facilitate chemoresistance progression. Transcriptome analysis of 142 HER2-negative breast cancer patients undergoing anthracycline-based chemotherapy revealed four distinct tumor-infiltrating cell subtypes, with subtype D exhibiting elevated M1 macrophage infiltration and superior prognostic outcomes. Differential expression analysis identified miR-222 as the predominantly upregulated microRNA in adriamycin-resistant cells, while Tandem Mass Tag mass spectrometry-based quantitative analysis elucidated PTEN as its direct target and FN1 as a crucial downstream mediator. Engineered extracellular vesicles (EVs) carrying a miR-222 inhibitor were developed to reverse adriamycin resistance via PTEN/FN1 signaling modulation. Molecular docking analysis found specific PTEN-FN1 protein interactions characterized by stable hydrogen bonds at ARG142-ASP23 and ARG15-GLU95. In xenograft models, EVs-mediated delivery of the miR-222 inhibitor significantly attenuated MCF-7/ADR tumor progression through miR-222 suppression and PTEN restoration, with concordant molecular alterations observed in serum-derived EVs. Our findings establish a novel mechanism of EVs-mediated drug resistance through the microRNA-222/PTEN/FN1 axis and present Engineered EVs as a promising therapeutic strategy for anthracycline resistance in breast cancer, while highlighting circulating EVs profiles as potential treatment monitoring biomarkers.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 9","pages":"2547-2567"},"PeriodicalIF":4.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}