Journal of Experimental & Clinical Cancer Research最新文献

{"title":"Upfront blood microRNA test in LDCT-reluctant individuals: insights from the biomild trial.","authors":"Gabriella Sozzi, Federica Sabia, Luigi Rolli, Miriam Segale, Paola Suatoni, Anna Zanghi, Margherita Ruggirello, Alfonso Marchianò, Mattia Boeri, Ugo Pastorino","doi":"10.1186/s13046-025-03424-5","DOIUrl":"10.1186/s13046-025-03424-5","url":null,"abstract":"<p><strong>Background: </strong>Low-dose computed tomography (LDCT) lung cancer screening can reduce mortality in high-risk individuals, but many individuals with a heavy smoking history may be reluctant to undergo radiologic examinations. A non-invasive blood test might help overcome this barrier. The BioMILD trial evaluated the combination of a plasma microRNA signature classifier (MSC) and LDCT for personalized lung cancer screening in 4,119 individuals who smoke or used to smoke. Based on BioMILD results, we aim to conduct a projection analysis to estimate the number of early lung cancers that could be detected if MSC were used as an initial screening tool for individuals reluctant to undergo LDCT. This model explores the potential of a biomarker-driven approach to address screening hesitation.</p><p><strong>Main body: </strong>The analysis focuses on 3,139 volunteers meeting NLST criteria. At baseline, 24.9% tested MSC-positive. Over two years, 63 lung cancer cases were detected, with a significantly higher incidence among MSC-positive participants (4.1% vs. 1.1%, p < 0.001). A biomarker-driven approach, where only MSC-positive individuals undergo annual LDCT, was compared to standard LDCT screening for all participants. This strategy could identify 58.7% of lung cancers detected via standard screening, including 56.5% of early-stage cases. Raw cost analysis estimated a per-case lung cancer detection cost of ~€14,000 for the biomarker-driven strategy versus ~€12,000 for standard screening.</p><p><strong>Conclusion: </strong>Upfront blood MSC test showed a reasonable sensitivity for lung cancer detection, including in early-stage disease, with affordable costs. Such a non-invasive blood test strategy might contribute to improve lung cancer screening endorsement in the high-risk population.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"168"},"PeriodicalIF":11.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: β-catenin-mediated YAP signaling promotes human glioma growth.","authors":"Yan Wang, Peng Pan, Zhaohao Wang, Yu Zhang, Peng Xie, Decheng Geng, Yang Jiang, Rutong Yu, Xiuping Zhou","doi":"10.1186/s13046-025-03415-6","DOIUrl":"10.1186/s13046-025-03415-6","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"169"},"PeriodicalIF":11.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: CD36 enrichment in HER2-positive mesenchymal stem cells drives therapy refractoriness in breast cancer.","authors":"Lorenzo Castagnoli, Alma Franceschini, Valeria Cancila, Matteo Dugo, Martina Bigliardi, Claudia Chiodoni, Paolo Toneguzzo, Viola Regondi, Paola A Corsetto, Filippo Pietrantonio, Serena Mazzucchelli, Fabio Corsi, Antonino Belfiore, Andrea Vingiani, Giancarlo Pruneri, Francesca Ligorio, Mario P Colombo, Elda Tagliabue, Claudio Tripodo, Claudio Vernieri, Tiziana Triulzi, Serenella M Pupa","doi":"10.1186/s13046-025-03426-3","DOIUrl":"10.1186/s13046-025-03426-3","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"165"},"PeriodicalIF":11.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CHD1L in cancer and beyond: structure, oncogenic functions, and therapeutic potential.","authors":"Sophia Clune, Paul Awolade, Hector Esquer, Qiong Zhou, Daniel V LaBarbera","doi":"10.1186/s13046-025-03428-1","DOIUrl":"10.1186/s13046-025-03428-1","url":null,"abstract":"<p><p>Chromodomain Helicase DNA-binding protein 1-Like (CHD1L) is a chromatin remodeling enzyme increasingly recognized as an oncogenic factor promoting tumor progression and metastatic potential by orchestrating transcriptional programs that drive epithelial-mesenchymal transition (EMT), cytoskeletal remodeling, and metastatic dissemination. In parallel, CHD1L has emerged as a master regulator of tumor cell survival by regulating DNA damage response and repair and enforcing G1 cell cycle progression. Furthermore, CHD1L plays a key role in immune evasion pathways by regulating signaling cascades and by suppressing both apoptotic and non-apoptotic cell death. In particular, CHD1L is a key suppressor of PARthanatos, a caspase-independent mechanism triggered by poly(ADP-ribose) (PAR) polymer fragmentation and apoptosis-inducing factor (AIF) activation. By regulating SPOCK1, MDM2, and TCTP, CHD1L further supports survival under cellular stress. Its overexpression correlates with metastasis, therapy resistance, and poor prognosis across many solid tumors. This review covers CHD1L's structure, oncogenic functions, and developmental origins, and highlights emerging therapeutic strategies that target CHD1L as a druggable vulnerability in cancer.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"167"},"PeriodicalIF":11.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Liquid biopsy in gynecological cancers: a translational framework from molecular insights to precision oncology and clinical practice.","authors":"Canio Martinelli, Alfredo Ercoli, Giuseppe Vizzielli, Sharon Raffaella Burk, Maria Cuomo, Vrunda Satasiya, Housem Kacem, Simone Braccia, Giulio Mazzarotti, Irene Miriello, Manuela Nana Tchamou, Stefano Restaino, Martina Arcieri, Alice Poli, Veronica Tius, Silvana Parisi, Stefano Pergolizzi, Giuseppe Iatì, Chiara Conti Nibali, Cristina Pizzimenti, Ludovica Pepe, Antonio Ieni, Salvatore Cortellino, Antonio Giordano","doi":"10.1186/s13046-025-03429-0","DOIUrl":"10.1186/s13046-025-03429-0","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"166"},"PeriodicalIF":11.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-inhibition of Notch1 and ChK1 triggers genomic instability and melanoma cell death increasing the lifespan of mice bearing melanoma brain metastasis.","authors":"Varsha Thakur, Vijay S Thakur, Dazhi Wang, Juliano Tiburcio de Freitas, Anna Bianchi, Luis Alberto Nivelo, Oliver Umland, Scott M Welford, Barbara Bedogni","doi":"10.1186/s13046-025-03411-w","DOIUrl":"10.1186/s13046-025-03411-w","url":null,"abstract":"<p><strong>Background: </strong>Melanoma brain metastases (MBM) are a leading cause of death in patients with advanced disease. MBM treatment relay on targeted and immunotherapy and on stereotactic radiosurgery as gold standard. Life expectancy has improved significantly with these therapies however, targeted therapy is short lived and only about half of the patients respond to immunotherapy, while radiation is limited by melanoma cells intrinsic resistance to DNA damage. New therapeutic approaches are therefore needed to treat MBM. Here we investigate a new role of Notch1 in genomic instability and demonstrate that blockade of both Notch1 and the DNA repair factor ChK1 causes extensive DNA damage and tumor cell death increasing survival in MBM bearing mice.</p><p><strong>Methods: </strong>Anti-Notch1 (anti-N1) was previously described. Prexaserib, a ChK1 inhibitor, is currently in clinical trials. K457 and A375 melanoma cells were used. RNA sequencing was performed in K457 cells treated with anti-N1 and Gene Set Enrichment Analysis performed. DNA damage was evaluated by a DNA fiber assay to assess replication fork speed; and γH2AX foci count and neutral comet assay to quantify double strand breaks. Cell survival was evaluated by trypan blue and a colony formation assay. Luciferase expressing A375 cells were orthotopically inoculated in the right cerebral cortex of athymic nude mice, for in vivo evaluation of a therapy with anti-N1 and prexasertib. Survival was assessed by Kaplan-Meyer survival curves and significance assessed by a Log-rank test.</p><p><strong>Results: </strong>Notch1 blockade caused genomic instability by reducing histone availability, leading to DNA replication stress and DNA damage. This in turn, resulted in the activation of the DNA Damage Response pathway ATR/ChK1 to counter the damage. Co-inhibition of Notch1, via anti-N1, and ChK1, via prexasertib (prex), exacerbated DNA damage increasing melanoma cell death. Importantly, combination anti-N1/prex significantly improved survival of mice bearing MBMs.</p><p><strong>Conclusions: </strong>A therapy with anti-N1/prexasertib could represent a novel treatment strategy, alone or in combination with current treatment regimens, for melanoma brain metastases.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"163"},"PeriodicalIF":11.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetylation-induced degradation of ECHS1 enhances BCAA accumulation and proliferation in KRAS-mutant colorectal cancer.","authors":"Zhenkang Li, Zhengyu Liu, Mingdao Lin, Huayang Pan, Yuechen Liu, Yang Liu, Yuwen Xie, Jinchao Zhang, Shenyuan Guan, Yongsheng Li, Mulan Zhu, Yuan Fang, Zhiyong Shen, Haijun Deng","doi":"10.1186/s13046-025-03399-3","DOIUrl":"10.1186/s13046-025-03399-3","url":null,"abstract":"<p><strong>Background: </strong>Branched-chain amino acid (BCAA) metabolism is dysregulated in colorectal cancer (CRC), with elevated plasma BCAA levels significantly associated with an increased risk of developing the disease. However, whether BCAAs directly promote CRC progression and their underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>In this study, we investigated the metabolic alterations in KRAS-mutant CRC. We examined the effects of restricting BCAA supply on the proliferation and metastasis of KRAS-mutant CRC cells both in vitro and in vivo.</p><p><strong>Results: </strong>We found that in KRAS-mutant CRC, BCAAs and their metabolic products accumulate markedly. Restricting the BCAA supply specifically inhibits the proliferation of KRAS-mutant CRC cells but does not affect metastasis. In these cancer cells, enoyl-CoA hydratase-1 (ECHS1), a key enzyme in BCAA metabolism, is downregulated. Furthermore, BCAAs enhance the acetylation of lysine 204 on ECHS1, impairing its ability to bind enoyl-CoA and reducing its catalytic activity. This modification triggers the ubiquitination of ECHS1 and its subsequent degradation, diminishing BCAA catabolism and leading to its cellular accumulation. This accumulation activates the mTORC1 signaling pathway, which induces the transcriptional activation of downstream target proteins and promotes the malignant progression of CRC.</p><p><strong>Conclusions: </strong>Limiting BCAA intake not only suppresses tumor growth in KRAS-mutant CRC but also enhances the efficacy of the KRAS G12D inhibitor MRTX1133 and the monoclonal antibody bevacizumab. Our findings reveal a previously unknown regulatory mechanism of ECHS1 in CRC and offer new potential therapeutic targets.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"164"},"PeriodicalIF":11.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour-associated macrophage infiltration differs in meningioma genotypes, and is important in tumour dynamics.","authors":"Ting Zhang, Claire L Adams, Gyorgy Fejer, Emanuela Ercolano, Jonathan Cutajar, Juri Na, Felix Sahm, C Oliver Hanemann","doi":"10.1186/s13046-025-03419-2","DOIUrl":"10.1186/s13046-025-03419-2","url":null,"abstract":"<p><strong>Background: </strong>Meningiomas are the most common primary intracranial tumours, with clinical behaviours ranging from benign to highly aggressive forms. The World Health Organisation classifies meningiomas into various grades, guiding prognosis and treatment. While surgery is effective for low-grade meningiomas, certain grade 1 tumours, as well as grade 2, 3, and recurrent cases are more aggressive and require new therapeutic approaches. Immunotherapy shows promise, with early-stage clinical trials demonstrating encouraging results. The tumour microenvironment (TME), particularly tumour-associated macrophages (TAMs), plays a pivotal role in tumour progression. TAMs influence tumour growth, metastasis, and immune evasion. However, their role in meningiomas, especially in relation to genomic mutations, remains poorly understood. Understanding how genetic alterations affect the TME is critical for developing targeted immunotherapies.</p><p><strong>Methods: </strong>This study employed multiplex immunohistochemistry and bulk RNA sequencing to explore immune infiltration in genetically stratified meningioma tissues and matched three-dimensional (3D) spheroid models. We compared immune cell populations across parental tissues, two-dimensional (2D) monolayer cultures, and 3D spheroid models. In addition, co-culture experiments were conducted, introducing M2-polarised macrophages derived from peripheral blood mononuclear cells to study the interactions between immune cells and tumour cells.</p><p><strong>Results: </strong>Our findings revealed significant differences in the immune infiltration patterns associated with specific genotypes and methylation classes, especially M2-like TAMs. Notably, the 3D spheroid models more closely replicated the TME observed in parental tissues compared to traditional 2D monolayer cultures, offering a superior platform for immune infiltration studies. Furthermore, co-culture experiments demonstrated that M2-polarised macrophages could effectively infiltrate tumour cells, promote tumour cell proliferation while inhibiting invasion, suggesting IL-6-mediated signalling in tumour progression.</p><p><strong>Conclusions: </strong>These findings suggest that 3D co-culture models offer an excellent system for studying the role of immune cells, specifically TAMs, in meningioma progression. By providing a more accurate representation of the TME, these models can help identify novel immunotherapy strategies aimed at modulating the immune response within meningiomas. Ultimately, this approach may improve therapeutic outcomes and quality of life for patients with meningioma by enhancing the effectiveness of existing treatments or by offering new immunotherapeutic options.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"162"},"PeriodicalIF":11.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Targeted Inhibition of PDGFRA with avapritinib, markedly enhances lenvatinib efficacy in hepatocellular carcinoma in vitro and in vivo: clinical implications.","authors":"Bixing Zhao, Yang Zhou, Niangmei Cheng, Xiaoyuan Zheng, Geng Chen, Xin Qi, Xiangzhi Zhang, Fei Wang, Qiuyu Zhuang, Yehuda G Assaraf, Xiaolong Liu, Yingchao Wang, Yongyi Zeng","doi":"10.1186/s13046-025-03423-6","DOIUrl":"10.1186/s13046-025-03423-6","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"160"},"PeriodicalIF":11.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.","authors":"Liang Shan, Mingxu Gong, Dandan Zhai, Xiangyun Meng, Jianjun Liu, Xiongwen Lv","doi":"10.1186/s13046-025-03416-5","DOIUrl":"10.1186/s13046-025-03416-5","url":null,"abstract":"<p><p>Adenosine signaling pathway is a kind of signal regulation hub widely existing in human body, which is involved in a series of physiological processes such as energy supply of body cells. CD73 is a highly concerned signaling protein in purine adenosine pathway, and its role in tumor development and prognosis has been paid more and more attention in recent years, especially in hepatocellular carcinoma (HCC). In this paper, the specific mechanism by which CD73-adenosine signaling regulates tumor microenvironment (TME) of liver cancer tumors was analyzed in detail, highlighting the importance of this pathway as a therapeutic target to combat tumor immunosuppression and enhance the anti-tumor immune response to prevent and treat hepatocellular carcinoma (HCC). In addition, a variety of current targeted therapeutic strategies for adenosine metabolic pathways are summarized, including the development of new drugs in the stage of preclinical research and clinical trials, and the mechanism of action, implementation possibility, and clinical effects of these therapies are discussed. By summarizing the latest scientific research results, in this review, we attempt to paint a panorama of the mechanism of adenosine action in tumor immunotherapy, with the aim to provide a solid theoretical basis and practical guidance for subsequent research and clinical application, ultimately promoting the development of more accurate and efficient tumor immunotherapy.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"161"},"PeriodicalIF":11.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}