Journal of Experimental & Clinical Cancer Research最新文献

{"title":"ERG inhibition selectively sensitizes ERG-positive prostate cancer to radiation through DNA repair vulnerabilities and enhances response to androgen receptor inhibitors.","authors":"Ayham Moustafa, Mohamed E Elsesy, Bente Siebels, Jan Hahn, Su-Jung Oh-Hohenhorst, Carlotta Schudy, Thorsten Rieckmann, Susanne Burdak-Rothkamm, Derya Tilki, Tobias Maurer, Cordula Petersen, Kai Rothkamm, Gunhild von Amsberg, Carsten Bokemeyer, Hartmut Schlüter, Sabrina Köcher, Wael Y Mansour","doi":"10.1186/s13046-026-03854-9","DOIUrl":"https://doi.org/10.1186/s13046-026-03854-9","url":null,"abstract":"<p><strong>Background: </strong>ERG overexpression, driven by TMPRSS2-ERG gene fusion, occurs in ~ 50% of prostate cancers (PCa) and defines a molecular subtype with distinct therapeutic vulnerabilities. Radiotherapy (RT) is a cornerstone for localized and locally advanced PCa, yet substantial number of patients experience treatment failure. This study investigates whether direct ERG inhibition selectively impairs the resolution of DNA damage signaling and radiosensitizes ERG-positive PCa, providing a precision medicine strategy.</p><p><strong>Methods: </strong>ERG-positive VCaP cells, ERG-negative DU145/BPH1 cells, ex vivo patient PCa tissue slice cultures (TSCs, n = 14 from 10 patients), and patient-derived organoids (PDOs, n = 2) were treated with ERG inhibitors (ERGi-USU, VPC-18005) or ERG siRNA ± irradiation (2-6 Gy). DNA double-strand break (DSB) repair was assessed via γ H2AX/53BP1 immunofluorescence and pEJ-GFP reporter assay. Clonogenic survival was evaluated in 2D/3D assays. Label-free quantitative LC-MS/MS proteomics identified differentially regulated pathways, validated by immunoblotting. Promoter activity was measured using GLuc-ON™ Promoter Reporter plasmids.</p><p><strong>Results: </strong>Here, we show that direct ERG inhibition selectively delays the resolution of radiation-induced DSB-associated damage signals and reduces end-joining activity in ERG-positive models, leading to enhanced radiosensitivity. In ERG-positive VCaP cells, ex vivo patient PCa tissue slices, and patient-derived PCa organoids, treatment with ERG inhibitors or ERG-targeted siRNA significantly increased residual γH2AX/53BP1 foci and reduced clonogenic survival following irradiation, whereas ERG-negative tumors remained unaffected. Quantitative LC-MS/MS proteomics, confirmed by immunoblotting and promoter activity assay, revealed that ERG inhibition downregulates key PARP1-mediated end-joining pathway components, including PARP1, LIG3, XRCC1, and the end-resection factor MRE11. Functional assays showed that ERG and PARP inhibition converge on a common mechanism to block alternative end joining, whereas combined ERG and androgen receptor (AR) pathway inhibition further suppressed growth in ERG-positive PCa spheroids and PDOs, probably through metabolic reprogramming.</p><p><strong>Conclusions: </strong>These data position ERG as a master regulator of DNA repair vulnerabilities in PCa and provide a strong mechanistic rationale for clinical evaluation of ERG-directed radiosensitization and combination therapy strategies in molecularly defined ERG-positive disease.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13695281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149276585","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":"Editorial expression of concern: Hyper-activation of Aurora kinase a-pololike kinase 1-FOXM1 axis promotes chronic myeloid leukemia resistance to tyrosine kinase inhibitors.","authors":"M Mancini, S De Santis, C Monaldi, L Bavaro, M Martelli, F Castagnetti, G Gugliotta, G Rosti, M A Santucci, G Martinelli, M Cavo, S Soverini","doi":"10.1186/s13046-026-03848-7","DOIUrl":"10.1186/s13046-026-03848-7","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170481","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: Efficient targeted tumor imaging and secreted endostatin gene delivery by antiCD105 immunoliposomes.","authors":"Huiqin Zhuo, Baoshi Zheng, Jianming Liu, Yong Huang, Huiling Wang, Duo Zheng, Naiquan Mao, Jinyu Meng, Sufang Zhou, Liping Zhong, Yongxiang Zhao","doi":"10.1186/s13046-026-03846-9","DOIUrl":"10.1186/s13046-026-03846-9","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139084","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":"Retraction Note: NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation.","authors":"Lei Yin, Wenjia Li, Guangchun Wang, Heng Shi, Keyi Wang, Huan Yang, Bo Peng","doi":"10.1186/s13046-026-03839-8","DOIUrl":"10.1186/s13046-026-03839-8","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129098","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: Galectin-3 induces pathogenic immunosuppressive macrophages through interaction with TREM2 in lung cancer.","authors":"Qiaohua Wang, Yongjian Wu, Guanmin Jiang, Xi Huang","doi":"10.1186/s13046-026-03831-2","DOIUrl":"https://doi.org/10.1186/s13046-026-03831-2","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117615","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":"Retraction Note: Regulation of TRIM24 by miR-511 modulates cell proliferation in gastric cancer.","authors":"Ling Zhang, Quan Liao, Yi Wang, Feng Yu, Miao Feng, Xiaojun Xiang, Jianping Xiong","doi":"10.1186/s13046-026-03838-9","DOIUrl":"https://doi.org/10.1186/s13046-026-03838-9","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117684","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":"Retraction Note: SULF2 overexpression positively regulates tumorigenicity of human prostate cancer cells.","authors":"Carolina M Vicente, Marcelo A Lima, Helena B Nader, Leny Toma","doi":"10.1186/s13046-026-03833-0","DOIUrl":"10.1186/s13046-026-03833-0","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031774","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":"CXCL9-driven immune rewiring and tumor-intrinsic ATR signaling inhibition restore radiotherapy response in lung cancer.","authors":"Sergio Leon, Nerea Otegui, Miriam Redrado, Eric Michel Marchena-Perea, Elisabeth Guruceaga, Flavia Castro, Luis M Montuenga, María José Oliveira, José Javier Aristu, Diego Serrano, Alfonso Calvo","doi":"10.1186/s13046-026-03834-z","DOIUrl":"10.1186/s13046-026-03834-z","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) accounts for ~ 85% of lung cancers and is associated with poor outcomes in advanced stages. Radiotherapy (RT) is central to NSCLC treatment, yet locoregional relapse remains frequent. Increasing evidence indicates that, beyond tumor-intrinsic adaptations, the tumor microenvironment (TME) and immune contexture critically influence response to irradiation. However, most radioresistance models rely on human cell lines unsuitable for immunocompetent systems, limiting insight into immune-tumor interactions.</p><p><strong>Methods: </strong>We generated radioresistant (RR) isogenic variants of murine lung adenocarcinoma cell lines and investigated RT resistance using transcriptomics, 3D co-culture systems, and syngeneic mouse models.</p><p><strong>Results: </strong>RR clones showed stable adaptations to DNA damage, including enhanced clonogenic survival, reduced immunogenic cell death, and constitutive activation of DNA damage response pathways, particularly ATR signaling. High ATR levels in NSCLC patients were significantly associated with immunosuppression. Transcriptomics revealed altered DNA repair and downregulation of type-I interferon and innate immune pathways. In vivo, RR tumors exhibited an immunosuppressive TME with increased T regulatory cells, M2-like macrophages, and myeloid-derived suppressor cells, alongside reduced cytotoxic T cell recruitment. In 3D co-cultures, immunosuppressive cells protected cancer cells from RT-induced cytotoxicity. Notably, RR tumors regained RT sensitivity in immunodeficient mice, highlighting the role of immune suppression in radioresistance. Therapeutically, activation of innate immunity using TLR3-TLR7/8 agonists (poly(I:C)+R848) restored antitumor responses and improved RT efficacy, partly via CXCL9/10-mediated immune recruitment. ATR inhibition with ceralasertib further sensitized RR tumors to RT.</p><p><strong>Conclusion: </strong>These findings identify cancer cell-intrinsic ATR signaling and immune suppression as key drivers of radioresistance and support combined therapeutic strategies to prevent locoregional relapse in NSCLC after radiotherapy.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185769","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: B7-H3 CAR T cells eradicate intrahepatic cholangiocarcinoma and induce durable response.","authors":"Shahrzad Arya, Marco Ventin, Giulia Cattaneo, Martina Nebbia, Seyed Amir Sanatkar, Cristina Martin, Jingyu Jia, Bangjin Kim, Cedric A Bailey, Nabeel M Bardeesy, David T Ting, Vikram Deshpande, Xinhui Wang, Sandra Ryeom, Soldano Ferrone, Cristina R Ferrone","doi":"10.1186/s13046-026-03825-0","DOIUrl":"10.1186/s13046-026-03825-0","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002772","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: Novel covalent CDK7 inhibitor potently induces apoptosis in acute myeloid leukemia and synergizes with Venetoclax.","authors":"Tarang Gaur, Ramulu Poddutoori, Leena Khare, Bhausaheb Bagal, Sonal Rashmi, Nikhil Patkar, Prashant Tembhare, Subramanian Pg, Dhanlaxmi Shetty, Amit Dutt, Qi Zhang, Marina Konopleva, Uwe Platzbeckar, Sueep Gupta, Susanta Samajdar, Murali Ramchandra, Navin Khattry, Syed K Hasan","doi":"10.1186/s13046-026-03824-1","DOIUrl":"10.1186/s13046-026-03824-1","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"45 1","pages":""},"PeriodicalIF":14.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002713","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}