Molecular Oncology最新文献

CDK11 inhibition induces cytoplasmic p21^WAF1 splice variant by p53 stabilisation and SF3B1 inactivation. CDK11抑制通过p53稳定和SF3B1失活诱导细胞质p21WAF1剪接变异。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-17 DOI: 10.1002/1878-0261.70143

Radovan Krejcir, Lukasz Arcimowicz, Lucia Martinkova, Vaclav Hrabal, Filip Zavadil Kokas, Tomas Henek, Martina Kucerikova, Ondrej Bonczek, Pavlina Zatloukalova, Lenka Hernychova, Philip J Coates, Borivoj Vojtesek, David P Lane

{"title":"CDK11 inhibition induces cytoplasmic p21WAF1 splice variant by p53 stabilisation and SF3B1 inactivation.","authors":"Radovan Krejcir, Lukasz Arcimowicz, Lucia Martinkova, Vaclav Hrabal, Filip Zavadil Kokas, Tomas Henek, Martina Kucerikova, Ondrej Bonczek, Pavlina Zatloukalova, Lenka Hernychova, Philip J Coates, Borivoj Vojtesek, David P Lane","doi":"10.1002/1878-0261.70143","DOIUrl":"https://doi.org/10.1002/1878-0261.70143","url":null,"abstract":"CDK11 is a cyclin-dependent kinase with a role in transcription and RNA splicing and represents a potential target for cancer treatment. We show that blocking CDK11 activity with the OTS964 inhibitor causes p53 stabilisation through MDM2 downregulation. Under these conditions, p53 activates the expression of its downstream effector CDKN1A (p21WAF1), produced in two isoforms, the canonical p21C and the recently described p21L. We compared the ability of both isoforms to block proliferation and showed that p21L partially lost its inhibitory potential, likely due to the missing cyclin-binding Cy2 and PCNA-interacting motifs and its cytoplasmic localisation. We identified the epitopes of four p21WAF1 antibodies using phage display to determine isoform specificity. Moreover, we show that the trigger for p21L induction is inhibition of the spliceosomal protein SF3B1. CDK11 activates SF3B1 by phosphorylation, and inhibition of either SF3B1 or CDK11 induces p21L. We discovered an isoform similar to human p21L in murine cells, suggesting evolutionary conservation of CDKN1A alternative splicing. Our results uncover an unknown link between RNA splicing and proliferation control involving a novel isoform of a key cell cycle inhibitor.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Reduced vascular leakage correlates with breast carcinoma T regulatory cell infiltration but not with metastatic propensity. 减少血管渗漏与乳腺癌T调节细胞浸润相关，但与转移倾向无关。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-16 DOI: 10.1002/1878-0261.70144

Liqun He, Chiara Testini, Neda Hekmati, Altea Bonello, Aglaia Schiza, Emmanuel Nwadozi, Mia Phillipson, Carina Strell, Michael Welsh

{"title":"Reduced vascular leakage correlates with breast carcinoma T regulatory cell infiltration but not with metastatic propensity.","authors":"Liqun He, Chiara Testini, Neda Hekmati, Altea Bonello, Aglaia Schiza, Emmanuel Nwadozi, Mia Phillipson, Carina Strell, Michael Welsh","doi":"10.1002/1878-0261.70144","DOIUrl":"https://doi.org/10.1002/1878-0261.70144","url":null,"abstract":"The vasculature and the immune system both play roles in breast cancer progression and metastasis. In an experimental mouse model of Shb-gene deficiency in endothelial cells, breast cancer lung metastasis correlated with immune suppression rather than with vascular leakage. The present study aimed to assess underlying gene expression changes in endothelial and immune cells responsible for this phenotype and to explore their relationship to human disease. Mouse endothelial cell Shb-gene deficiency, leading to 'vessel normalization', resulted in altered expression of chemo/cytokine genes and upregulation of immune checkpoint genes in immune cells. Endothelial cells under these conditions exhibited gene expression patterns compatible with reduced angiogenesis and vascular leakage. Additionally, genes whose products relate to immune cell vascular transmigration and function were affected. In a human triple-negative breast cancer cohort, tumors with reduced vascular leakage exhibited a higher relative proportion of regulatory T cells and larger tumor size. However, these changes were not associated with increased metastasis. In conclusion, a low leakage vascular phenotype reduces tumor cell intravasation/metastasis and modifies the immune response, which in the current context becomes pro-tumoral.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A synthetic benzoxazine dimer derivative targets c-Myc to inhibit colorectal cancer progression. 合成苯并恶嗪二聚体衍生物靶向c-Myc抑制结直肠癌进展。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-14 DOI: 10.1002/1878-0261.70127

Nicharat Sriratanasak, Bodee Nutho, Worawat Wattanathana, Narumon Phaonakrop, Bunnatut Panasawatwong, Katharina Erlenbach-Wuensch, Sittiruk Roytrakul, Regine Schneider-Stock, Pithi Chanvorachote

{"title":"A synthetic benzoxazine dimer derivative targets c-Myc to inhibit colorectal cancer progression.","authors":"Nicharat Sriratanasak, Bodee Nutho, Worawat Wattanathana, Narumon Phaonakrop, Bunnatut Panasawatwong, Katharina Erlenbach-Wuensch, Sittiruk Roytrakul, Regine Schneider-Stock, Pithi Chanvorachote","doi":"10.1002/1878-0261.70127","DOIUrl":"https://doi.org/10.1002/1878-0261.70127","url":null,"abstract":"The c-Myc protein is a well-known oncoprotein that plays a crucial role in regulating cell growth, proliferation, and differentiation. The overexpression or dysregulation of c-Myc is commonly associated with tumorigenesis in several cancers, including colorectal cancer (CRC). c-Myc forms a heterodimer with its partner MAX to activate the expression of various genes. Here, we synthesized a novel c-Myc-targeting small molecule, 2,2'-((cyclohexylazanedyl)bis(methylene))bis(4-ethylphenol), or ECD, and demonstrate ECD's anticancer activity via interference with the c-Myc/MAX dimer to promote c-Myc degradation in CRC cells in vitro, in silico, and in vivo. This study revealed the activity of ECD toward CRC cells as a c-Myc inhibitor. Computer-aided analysis revealed that the effect of ECD was mediated through disturbance of the c-Myc/MAX complex. Moreover, ECD exhibited cytotoxic activity by inducing DNA damage, leading to apoptotic cell death. This DNA damage-inducing property was also confirmed by whole-proteome profiling of HT29 cells after ECD treatment. In the chick embryo chorioallantoic membrane (CAM) xenograft assay, we demonstrated a remarkable inhibition of the tumorigenic activity upon ECD exposure. In summary, we identified ECD as a novel potent compound targeting the oncoprotein c-Myc that may offer new opportunities for CRC treatment.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 IFNγ-CIITA-MHC II axis modulates melanoma cell susceptibility to NK-cell-mediated cytotoxicity. IFNγ-CIITA-MHC II轴调节黑色素瘤细胞对nk细胞介导的细胞毒性的易感性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-13 DOI: 10.1002/1878-0261.70133

Lena C M Krause, Rixa-Mareike Köhn, Christian Ickes, Julia Lenger, Jonas Fischer, Sabrina Cappello, Ivan Bogeski

{"title":"The IFNγ-CIITA-MHC II axis modulates melanoma cell susceptibility to NK-cell-mediated cytotoxicity.","authors":"Lena C M Krause, Rixa-Mareike Köhn, Christian Ickes, Julia Lenger, Jonas Fischer, Sabrina Cappello, Ivan Bogeski","doi":"10.1002/1878-0261.70133","DOIUrl":"https://doi.org/10.1002/1878-0261.70133","url":null,"abstract":"Melanoma, the deadliest form of skin cancer, poses a significant challenge due to its genetic heterogeneity and high metastatic potential. While cytotoxic T cell (CTL)-based immunotherapies have made remarkable progress in recent years, the therapeutic potential of natural killer-(NK) cells is increasingly recognized. However, resistance mechanisms to both CTL- and NK-cell-mediated immunotherapies hinder effective treatment. To evaluate the exclusive role of NK-cells in anti-melanoma immunity, we performed 2D and 3D co-culture-based cytotoxicity assays under varying conditions. Our findings revealed a protective phenotype in melanoma cells following prolonged exposure to primary NK-cells. By combining experimental data with bioinformatic analyses, we identified key genes and pathways involved in melanoma cell adaptation to NK-cell-mediated killing (NKmK). We found that cytokines such as IFNγ play a major role in suppressing NKmK with MHC II surface expression being a critical factor. Targeting the master regulator CIITA, which governs MHC II expression and is affected by IFNγ, significantly reduced melanoma cell resistance to NKmK. This study provides potential strategies to overcome resistance to NK-cell-based immunotherapies and offers novel insights into melanoma immune escape mechanisms.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Intein-based modular chimeric antigen receptor platform for specific CD19/CD20 co-targeting. 特异性CD19/CD20共靶向的基于内部蛋白的模块化嵌合抗原受体平台。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-13 DOI: 10.1002/1878-0261.70146

Pablo Gonzalez-Garcia, Noelia Moares, Wenjie Yi-He, Rosa Luna-Espejo, Ricardo Fernandez-Cisnal, Javier Ocaña-Cuesta, Juan P Muñoz-Miranda, Antonio Gabucio, Cecilia M Fernandez-Ponce, Francisco Garcia-Cozar

{"title":"Intein-based modular chimeric antigen receptor platform for specific CD19/CD20 co-targeting.","authors":"Pablo Gonzalez-Garcia, Noelia Moares, Wenjie Yi-He, Rosa Luna-Espejo, Ricardo Fernandez-Cisnal, Javier Ocaña-Cuesta, Juan P Muñoz-Miranda, Antonio Gabucio, Cecilia M Fernandez-Ponce, Francisco Garcia-Cozar","doi":"10.1002/1878-0261.70146","DOIUrl":"https://doi.org/10.1002/1878-0261.70146","url":null,"abstract":"Development of chimeric antigen receptor T-cell therapy has revolutionized the treatment of B-cell malignancies, although challenges such as antigen escape and tumor heterogeneity often decrease treatment success. Modular CARs targeting multiple antigens have been proposed as an interesting solution to address these challenges by reducing the likelihood of tumor cells evading treatment through the loss of a single antigen. In this study, we present a new modular CAR platform, termed CARtein, which takes advantage of intein interactions to jointly target CD19 and CD20 antigens. We demonstrate that the CARtein system, which features a universal CAR signaling backbone that covalently binds to specific scFv-intein recognition partners, generates fully active CARs. Functionality was validated using Raji cells and K562 cells expressing CD19 and/or CD20, observing significant T cell activation through NFAT and NFκB promoter activity and CD69 upregulation. Overall, our study lays the foundation for the establishment of a new way to target multiple antigens through a universal and inert CAR backbone with highly specific activation.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Survivin and Aurora Kinase A control cell fate decisions during mitosis. Survivin和极光激酶A控制有丝分裂过程中细胞命运的决定。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-12 DOI: 10.1002/1878-0261.70141

Hana Abdelkabir, Shalitha Wickrama Arachchige, Sally P Wheatley

{"title":"Survivin and Aurora Kinase A control cell fate decisions during mitosis.","authors":"Hana Abdelkabir, Shalitha Wickrama Arachchige, Sally P Wheatley","doi":"10.1002/1878-0261.70141","DOIUrl":"https://doi.org/10.1002/1878-0261.70141","url":null,"abstract":"The spindle assembly checkpoint (SAC) delays the metaphase-to-anaphase transition. Aurora kinase A (AURKA) inactivation has been shown to cause premature exit from mitosis in the presence of an unsatisfied SAC. We report for the first time that centromeric AURKA interacts with survivin during prometaphase. Notably, depleting or inhibiting AURKA activity at this stage causes mislocalisation of the CPC and BubR1, which compromises the SAC and can lead to mitotic slippage. Furthermore, we show that AURKA binds directly to the BIR domain of survivin at a position distinct from AURKB and indirectly to it via its C terminus. We find the interaction peaks during prometaphase but persists into late mitosis. Importantly, we demonstrate that cells with high levels of survivin are particularly vulnerable to mitotic slippage induced by the AURKA inhibitor, MLN8237/ Alisertib. Alisertib enables both normal and transformed cells with high levels of survivin to activate the APC/C prematurely, as observed by the destruction of cyclin B and securin. Thus, a high expression of survivin can alter cell fate decisions at mitosis and lead to genetic instability, a key hallmark in cancer.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Feasibility of a ctDNA multigenic panel for non-small-cell lung cancer early detection and disease surveillance. 用于非小细胞肺癌早期检测和疾病监测的ctDNA多基因面板的可行性

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-10 DOI: 10.1002/1878-0261.70131

Giovanna Maria Stanfoca Casagrande, Marcela de Oliveira Silva, Mariana Bisarro Dos Reis, Rodrigo de Oliveira Cavagna, Luciane Sussuchi, Icaro Alves Pinto, Natalia Zampieri Pontes, Rodrigo Sampaio Chiarantano, Flavio Augusto Ferreira da Silva, Pedro de Marchi, Letícia Ferro Leal, Rui M Reis

{"title":"Feasibility of a ctDNA multigenic panel for non-small-cell lung cancer early detection and disease surveillance.","authors":"Giovanna Maria Stanfoca Casagrande, Marcela de Oliveira Silva, Mariana Bisarro Dos Reis, Rodrigo de Oliveira Cavagna, Luciane Sussuchi, Icaro Alves Pinto, Natalia Zampieri Pontes, Rodrigo Sampaio Chiarantano, Flavio Augusto Ferreira da Silva, Pedro de Marchi, Letícia Ferro Leal, Rui M Reis","doi":"10.1002/1878-0261.70131","DOIUrl":"https://doi.org/10.1002/1878-0261.70131","url":null,"abstract":"The detection of actionable mutations in liquid biopsies is a crucial tool for precision oncology in patients with non-small-cell lung cancer (NSCLC). We evaluated actionable alterations using a multigene panel in circulating tumor DNA (ctDNA) from Brazilian NSCLC patients. We analyzed 32 samples from 30 patients with NSCLC, including four samples from a lung cancer screening program. ctDNA isolation and library preparation were performed using the Oncomine Lung cfDNA Assay, which covers 11 actionable genes, and sequenced on an Ion S5 Sequencer. The IonReporter 5.20 software was used for variant calling. Median read coverage reached 80 967, with a detection limit of 0.1%. TP53 (40.6%), KRAS (28.1%), and EGFR (12.5%) were the most frequently mutated genes, particularly in patients who had previously received treatment. BRAF, MAP2K1, PIK3CA, and ALK mutations were observed at lower frequencies (6.2%, 3.1%, 3.1%, and 3.1%, respectively). The EGFR p.T790M mutations related to resistance were identified in a patient who had been previously treated, and the TP53 p.R248Q mutation was discovered in an asymptomatic patient before diagnosis. No variants were observed in NRAS, ROS1, and MET genes. Our data showed that this commercial NGS panel could detect actionable mutations, enabling early detection, treatment monitoring, and disease surveillance.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Modeling hepatic fibrosis in TP53 knockout iPSC-derived human liver organoids. 在TP53敲除ipsc衍生的人肝类器官中模拟肝纤维化。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-09 DOI: 10.1002/1878-0261.70119

Mustafa Karabicici, Soheil Akbari, Ceyda Caliskan, Canan Celiker, Ozden Oz, Leman Binokay, Gökhan Karakulah, Serif Senturk, Esra Erdal

{"title":"Modeling hepatic fibrosis in TP53 knockout iPSC-derived human liver organoids.","authors":"Mustafa Karabicici, Soheil Akbari, Ceyda Caliskan, Canan Celiker, Ozden Oz, Leman Binokay, Gökhan Karakulah, Serif Senturk, Esra Erdal","doi":"10.1002/1878-0261.70119","DOIUrl":"https://doi.org/10.1002/1878-0261.70119","url":null,"abstract":"Hepatic fibrogenesis is characterized by the excessive accumulation of extracellular matrix proteins, ultimately predisposing to hepatocarcinogenesis. The lack of reliable models that faithfully recapitulate early stage fibrogenesis is one of the main limitations in identifying translationally relevant therapeutics. Here, we establish a model using CRISPR/Cas9-mediated TP53 knockout iPSC (endoderm)-derived human hepatic organoids (eHEPOs) to mimic human liver fibrosis. Transcriptomic profiling of TP53KO-eHEPOs revealed enrichment of pathways associated with inflammation, ECM remodeling, and fibrosis, with notable alterations in pivotal fibrotic regulators. We also find increased expression of myofibroblasts and fibrosis markers (PDGFRB, COL1A1, COL3A1, COL11A1) and early liver cancer markers (GPC3 and MUC1). Histological analysis confirmed advanced fibrotic hallmarks and exposure to an exogenous profibrotic environment (pf-ME) further enhanced these fibrotic phenotypes. This model provides a valuable platform for exploring the role of key driver genes, such as TP53, in the initiation and progression of fibrosis, enabling the study of hepatic progenitor cell transformation across diverse microenvironmental contexts. As such, it holds the potential for advancing early stage drug discovery and the identification of novel therapeutic targets for the treatment of liver fibrosis.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Glycosylated LGALS3BP is highly secreted by bladder cancer cells and represents a novel urinary disease biomarker. 糖化LGALS3BP由膀胱癌细胞高度分泌，是一种新的泌尿系统疾病生物标志物。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-05 DOI: 10.1002/1878-0261.70140

Asia Pece, Giulio Lovato, Ilaria Cela, Arianna Mercatelli, Benedetta Ferro, Jussi Nikkola, Sara Pagotto, Tommaso Grottola, Vincenzo De Laurenzi, Rossella Cicchetti, Antonio Marchetti, Luigi Schips, Rossano Lattanzio, Stefano Iacobelli, Emily Capone, Peter Black, Mads Daugaard, Michele Marchioni, Gianluca Sala

{"title":"Glycosylated LGALS3BP is highly secreted by bladder cancer cells and represents a novel urinary disease biomarker.","authors":"Asia Pece, Giulio Lovato, Ilaria Cela, Arianna Mercatelli, Benedetta Ferro, Jussi Nikkola, Sara Pagotto, Tommaso Grottola, Vincenzo De Laurenzi, Rossella Cicchetti, Antonio Marchetti, Luigi Schips, Rossano Lattanzio, Stefano Iacobelli, Emily Capone, Peter Black, Mads Daugaard, Michele Marchioni, Gianluca Sala","doi":"10.1002/1878-0261.70140","DOIUrl":"https://doi.org/10.1002/1878-0261.70140","url":null,"abstract":"Bladder cancer incidence has recently risen, making it the ninth most diagnosed cancer, highlighting an urgent need for novel and effective diagnostic and therapeutic strategies to improve patient outcomes. Here, we report on a secreted glycoprotein, Galectin-3-binding protein (LGALS3BP), as a potential biomarker and therapeutic target for bladder cancer. We found a significantly elevated LGALS3BP expression in bladder cancer tissues, correlating with disease progression. Moreover, urinary and serum levels of LGALS3BP were significantly higher in patients compared to healthy individuals, with a strong correlation observed between elevated urinary protein levels and tumor grade. Of note, LGALS3BP produced by tumor cells treated with a mannosidase I inhibitor, Kifunensine, exhibited increased reactivity to a therapeutic antibody (denoted as \"1959\"), suggesting that glycosylation of LGALS3BP may influence antibody recognition and protein function. Furthermore, administration of 1959-sss/DM4 antibody-drug conjugate in two xenograft mouse models of human bladder cancer resulted in complete inhibition of tumor growth. In summary, findings presented here highlight LGALS3BP as a promising candidate for further investigation into its potential as a urinary biomarker and a therapeutic target for bladder cancer.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 and germline testing with next generation sequencing in epithelial ovarian cancer: a prospective paired comparison using an 18-gene panel. 肿瘤和生殖系检测与下一代测序在上皮性卵巢癌：使用18基因面板的前瞻性配对比较。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2025-10-05 DOI: 10.1002/1878-0261.70136

Elisabeth Spenard, Cristina Mitric, Melanie Care, Tracy L Stockley, Raymond H Kim, Jeanna McCuaig, Blaise Clarke, Laura Ranich, Clare Sheen, Sarah E Ferguson, Liat Hogen, Taymaa May, Marcus Q Bernardini

{"title":"Tumor and germline testing with next generation sequencing in epithelial ovarian cancer: a prospective paired comparison using an 18-gene panel.","authors":"Elisabeth Spenard, Cristina Mitric, Melanie Care, Tracy L Stockley, Raymond H Kim, Jeanna McCuaig, Blaise Clarke, Laura Ranich, Clare Sheen, Sarah E Ferguson, Liat Hogen, Taymaa May, Marcus Q Bernardini","doi":"10.1002/1878-0261.70136","DOIUrl":"https://doi.org/10.1002/1878-0261.70136","url":null,"abstract":"Genetic testing in epithelial ovarian cancer (EOC) in Ontario includes germline next-generation sequencing (NGS) for 19 genes. Additionally, tumor tissue undergoes reflex NGS testing for BRCA1/2 to assess eligibility for PARPi. Although parallel testing confers advantages, this model duplicates healthcare resources. Here, we prospectively assessed the feasibility of tumor-first multigene testing by comparing tumor tissue with germline testing of peripheral blood. An 18-gene NGS panel was used to test tumor and germline DNA (n = 106 patients). In 26 patients, 27 tumor Tier I or II variants were identified, with 16/27 (59%) being germline pathogenic variants (PV) (13 BRCA1/2; 3 other genes) and 11/27 (41%) somatic variants (9 BRCA1/2; 2 other). In 51/106 patients, there were no tumor variants (excluding TP53), of which one patient had a germline BRCA1 copy number variant deletion in exon 12. Tumor-first testing detected variant-positive and variant-negative germline cases in 105/106 patients (99.1%). Among 50 BRCA-negative patients, 14/50 (28%) were homologous recombination deficiency (HRD)-positive. Therefore, we demonstrate that multigene NGS tumor-testing is effective in identifying germline variants in EOC with a < 1% false-negative rate.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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