Neoplasia最新文献_第2页

Targeting lysosomal protease CTSL promotes anti-tumor immunity and sensitizes HNSCC to PD-1 blockade by stabilizing PDK1 and activating Akt–PD-L1 axis 靶向溶酶体蛋白酶CTSL通过稳定PDK1和激活Akt-PD-L1轴，促进抗肿瘤免疫，并使HNSCC对PD-1阻断增敏。

IF 7.7 2区医学

Neoplasia Pub Date : 2025-09-16 DOI: 10.1016/j.neo.2025.101228

Yaodong Ding , Haoyu Zhang , Xueying Wang , Jiaqi Tan , Minghao Wang , Yuhan Chen , Imadoudini Hassimi Safia , Gangcai Zhu , Xin Zhang , Yong Liu

引用次数: 0

Corrigendum to “Single-cell proteomic analysis reveals Multiple Myeloma heterogeneity and the dynamics of the tumor immune microenvironment in precursor and advanced states” [Neoplasia 66 (2025) 1101189] “单细胞蛋白质组学分析揭示多发性骨髓瘤前体和晚期肿瘤免疫微环境的异质性和动力学”[Neoplasia 66(2025) 1101189]的勘误表

IF 7.7 2区医学

Neoplasia Pub Date : 2025-09-06 DOI: 10.1016/j.neo.2025.101226

Mohamed Kamal , Stephanie N. Shishido , Jeremy Mason , Krina Patel , Elisabet E. Manasanch , Robert Z. Orlowski , Peter Kuhn

引用次数: 0

Contribution of the immune bone marrow microenvironment to tumor growth and bone deconstruction: implications for improving immunotherapeutic strategies in bone metastasis 免疫骨髓微环境对肿瘤生长和骨解构的贡献：改善骨转移免疫治疗策略的意义

IF 7.7 2区医学

Neoplasia Pub Date : 2025-09-02 DOI: 10.1016/j.neo.2025.101224

E. Massy , C.B. Confavreux , M. Point , E. Bonnelye , P. Clézardin

{"title":"Contribution of the immune bone marrow microenvironment to tumor growth and bone deconstruction: implications for improving immunotherapeutic strategies in bone metastasis","authors":"E. Massy , C.B. Confavreux , M. Point , E. Bonnelye , P. Clézardin","doi":"10.1016/j.neo.2025.101224","DOIUrl":"10.1016/j.neo.2025.101224","url":null,"abstract":"<div><div>Bone metastases are frequent complications of many solid tumors, leading to painful skeletal morbidities and increasing mortality for patients with advanced cancer. Once in bone, cancer cells deregulate bone homeostasis, altering the functions of bone-forming (osteoblasts) and bone-resorbing (osteoclasts) cells, which results in skeletal deconstruction. Aside from bone cells, cancer cells in the bone marrow interact with other cell populations, including immune cells that also play an integral part in the regulation of bone homeostasis. In this respect, immune checkpoint inhibitors (ICIs) have become a standard of care in immunotherapy for the treatment of patients with advanced cancer. Strikingly, however, those with bone metastases have a shorter survival when treated with ICIs than ICI-treated cancer patients without bone metastases. In this Review, after presenting the immune cells involved in bone metastasis, we review preclinical and clinical findings assessing ICI efficacy both in bone and extraosseous metastases, and we discuss the clinical utility of using bone-targeted agents —including denosumab and bisphosphonates— to improve anti-tumoral efficacy of ICI treatments in patients with cancer and bone metastases.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101224"},"PeriodicalIF":7.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933442","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

Steatohepatitis alters lymphocytes cytotoxicity and localization, accelerating colorectal liver metastases 脂肪性肝炎改变淋巴细胞的细胞毒性和定位，加速结直肠肝转移

IF 7.7 2区医学

Neoplasia Pub Date : 2025-08-28 DOI: 10.1016/j.neo.2025.101222

Adi S. Yehezkel , Eyal Yehezkel , Nathalie Abudi , Rinat Abramovitch

{"title":"Steatohepatitis alters lymphocytes cytotoxicity and localization, accelerating colorectal liver metastases","authors":"Adi S. Yehezkel , Eyal Yehezkel , Nathalie Abudi , Rinat Abramovitch","doi":"10.1016/j.neo.2025.101222","DOIUrl":"10.1016/j.neo.2025.101222","url":null,"abstract":"<div><h3>Background & Aims</h3><div>The liver is the most common site for distant metastasis. Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease worldwide and significantly increases the risk of liver metastasis in colorectal cancer (CRC) patients. We aimed to elucidate hepatic immune cells alterations in response to the metabolic stress in MAFLD and their influence on the early stages of CRC liver metastasis (CRLM).</div></div><div><h3>Methods</h3><div>High-fat diet (HFD) and Western diet (WD), were used to create MAFLD and MASH respectively. MC38 cancer cells were injected intrasplenically to create CRLM model. Single-cell RNA sequencing (scRNA-seq), RT-PCR and immunohistology were used to study hepatic immune-cell composition, phenotypes, and localization.</div></div><div><h3>Results</h3><div>Both diets significantly increased CRLM establishment, while only WD altered hepatic inflammation. The WD-promotes IL-10 and TGF-β1 elevation, an anti-inflammatory cytokines, inhibiting cytotoxic CD8<sup>+</sup> T cells and NK cells and supporting an immunosuppressive environment. Although MASH led to an increased presence of hepatic CD8<sup>+</sup> and NK cells, their infiltration into metastatic foci was reduced and was associated with a decrease in expression of cytotoxic markers. In our murine model of MASH, CD8<sup>+</sup> T-cell depletion reduced the number of CRLM foci, which was accompanied by a decrease in IFN-γ-associated cytokines and a significant increase in the infiltration of granzyme-B expressing NK cells, ultimately enhancing cytotoxic killing ability.</div></div><div><h3>Conclusions</h3><div>This research underscores the crucial influence of diet-induced immune changes on CRLM establishment and progression. It illustrates that the co-localization of immune cells within liver metastases significantly affects their functionality, highlighting potential therapeutic strategies to balance immune exhaustion and activation.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101222"},"PeriodicalIF":7.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907856","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 methyl-to-acetyl switch in H3K27 drives metabolic reprogramming and resistance to BRAFV600E inhibition in melanoma 在黑色素瘤中，H3K27中的甲基-乙酰开关驱动代谢重编程和对BRAFV600E抑制的抗性

IF 7.7 2区医学

Neoplasia Pub Date : 2025-08-23 DOI: 10.1016/j.neo.2025.101223

Jiang Zhou , Xinxin Chai , Yi Zhu , Zhi Huang , Tingting Lin , Zhen Hu , Guangdi Chen , Chi Luo , Rutao Cui , Jinghao Sheng

{"title":"A methyl-to-acetyl switch in H3K27 drives metabolic reprogramming and resistance to BRAFV600E inhibition in melanoma","authors":"Jiang Zhou , Xinxin Chai , Yi Zhu , Zhi Huang , Tingting Lin , Zhen Hu , Guangdi Chen , Chi Luo , Rutao Cui , Jinghao Sheng","doi":"10.1016/j.neo.2025.101223","DOIUrl":"10.1016/j.neo.2025.101223","url":null,"abstract":"<div><div>The BRAF<sup>V600E</sup> pathway and epigenetic machinery are central to melanoma pathogenesis. However, how these processes intersect and their potential for synthetic lethality remains unclear. Here, we identified a BRAF<sup>V600E</sup>-driven epigenetic mechanism in melanoma that involves a H3K27 methylation-to-acetylation switch, facilitating metabolic adaptation to targeted therapies. Inhibition of BRAF<sup>V600E</sup> downregulates the methyltransferase EZH2, leading to KDM6A-mediated removal of H3K27me3 and a subsequent increase in H3K27 acetylation (H3K27ac). This H3K27 methyl-to-acetyl conversion shifts chromatin from a repressive to an active state, thereby promoting gene transcription through the acetylation reader BRD4. Specifically, the KDM6A-H3K27ac-BRD4 axis upregulates PGC1α, a master regulator of mitochondrial metabolism, enabling melanoma cells to sustain oxidative metabolism and survive BRAF<sup>V600E</sup>-targeted therapies. Blocking this H3K27 methyl-to-acetyl switch disrupted metabolic adaptation and sensitized melanoma cells to BRAF<sup>V600E</sup> inhibition. In conclusion, we revealed an epigenetic and metabolic reprogramming mechanism that enables melanoma to survive the treatment with BRAF<sup>V600E</sup> inhibitors, presenting druggable targets within the H3K27 modification pathway that could enhance the efficacy of BRAF-targeted therapies in melanoma patients.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101223"},"PeriodicalIF":7.7,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892261","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

Neuropilin-2 upregulation by stromal TGFβ1 induces lung disseminated tumor cells dormancy escape and promotes metastasis outgrowth 间质tgf - β1上调Neuropilin-2诱导肺弥散性肿瘤细胞休眠逃逸，促进转移生长

IF 7.7 2区医学

Neoplasia Pub Date : 2025-08-22 DOI: 10.1016/j.neo.2025.101220

L Recalde-Percaz , I de la Guia-Lopez , P Linzoain-Agos , A Noguera-Castells , M Rodrigo-Faus , P Jauregui , A Lopez-Plana , P Fernández-Nogueira , M Iniesta-González , M Cueto-Remacha , S Manzano , R Alonso , N Moragas , C Baquero , N Palao , E Dalla , FX Avilés-Jurado , I Vilaseca , X León-Vintró , M Camacho , P Bragado

{"title":"Neuropilin-2 upregulation by stromal TGFβ1 induces lung disseminated tumor cells dormancy escape and promotes metastasis outgrowth","authors":"L Recalde-Percaz , I de la Guia-Lopez , P Linzoain-Agos , A Noguera-Castells , M Rodrigo-Faus , P Jauregui , A Lopez-Plana , P Fernández-Nogueira , M Iniesta-González , M Cueto-Remacha , S Manzano , R Alonso , N Moragas , C Baquero , N Palao , E Dalla , FX Avilés-Jurado , I Vilaseca , X León-Vintró , M Camacho , P Bragado","doi":"10.1016/j.neo.2025.101220","DOIUrl":"10.1016/j.neo.2025.101220","url":null,"abstract":"<div><div>Metastasis is the main cause of death from solid tumors. Therefore, identifying the mechanisms that govern metastatic growth poses a major biomedical challenge. Tumor microenvironment signals regulate the fate and survival of disseminated tumor cells (DTCs) in secondary organs. However, very little is known about the role of nervous system mediators in this process. We have previously reported that neuropilin-2 (NRP2) expression in breast cancer correlates with poor prognosis. Here, we show that NRP2 positively regulates the proliferation, invasion, and survival of breast and head and neck cancer cells <em>in vitro</em>. NRP2 deletion in tumor cells inhibits tumor growth <em>in vivo</em> and decreases the number and size of lung metastases by promoting lung DTCs quiescence. NRP2 deletion upregulates dormancy and cell cycle regulators expression and promotes DTCs reprograming into quiescence. Moreover, lung fibroblasts and macrophages induce NRP2 upregulation in DTCs through the secretion of TGFβ1. NRP2 facilitates lung DTC interaction with the extracellular matrix and promotes lung DTCs activation and metastasis. Therefore, we conclude that the TGFβ1-NRP2 axis is a new key dormancy-awakening inducer that promotes DTCs proliferation and lung metastasis development.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101220"},"PeriodicalIF":7.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886248","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

Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition 基于运动的体外培养（MOTEX）乳房肿瘤切片维持微环境组成

IF 7.7 2区医学

Neoplasia Pub Date : 2025-08-21 DOI: 10.1016/j.neo.2025.101221

Zofia M. Komar , Mieke Bavelaar , Ellen Kageler , Nicole S. Verkaik , Mandy M. van Rosmalen , Carolien H.M. van Deurzen , Michael A. den Bakker , Roland Kanaar , Adriaan B Houtsmuller , Thierry P.P. van den Bosch , Agnes Jager , Dik C. van Gent

{"title":"Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition","authors":"Zofia M. Komar , Mieke Bavelaar , Ellen Kageler , Nicole S. Verkaik , Mandy M. van Rosmalen , Carolien H.M. van Deurzen , Michael A. den Bakker , Roland Kanaar , Adriaan B Houtsmuller , Thierry P.P. van den Bosch , Agnes Jager , Dik C. van Gent","doi":"10.1016/j.neo.2025.101221","DOIUrl":"10.1016/j.neo.2025.101221","url":null,"abstract":"<div><div>Personalized medicine for breast cancer (BrC) requires predictive biomarkers to select the optimal therapeutic option for each individual patient. Personalization of chemotherapy or immunotherapy responses is particularly challenging, as molecular markers do not appear to be sufficiently predictive for therapy response. Functional assays for therapy selection may be the solution for this dilemma. An interesting approach is <em>ex vivo</em> cultures of precision cut tumor slices, such as the MOtion-based Tissue EX vivo (MOTEX) method that we described previously. This culture method has the advantage that it carries all cell types in the tumor, including various immune cell populations. We here show, that macrophages, B-cells and T-cell populations are maintained in the MOTEX culture for several days without apparent loss of viability. Even treatment with the microtubule poison paclitaxel did not reduce immune cell abundance or viability significantly. Anthracycline-based chemotherapy, however, did affect immune cell composition, as expected based on its cytotoxic properties. Therefore, we conclude that MOTEX culture of BrC tissue slices can be used to investigate effect of treatments that involve the immune system. This opens perspectives to develop predictive assays for immune checkpoint inhibitor treatment and other therapeutic interventions that require immune components in the assay system.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101221"},"PeriodicalIF":7.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879604","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

Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis Prkci激活Jak2/Stat3信号，促进肿瘤血管生成

IF 7.7 2区医学

Neoplasia Pub Date : 2025-08-20 DOI: 10.1016/j.neo.2025.101219

Peng Li , Guangshi Liu , Wenbin Zhang , Tao Li , Xinhui Yang

{"title":"Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis","authors":"Peng Li , Guangshi Liu , Wenbin Zhang , Tao Li , Xinhui Yang","doi":"10.1016/j.neo.2025.101219","DOIUrl":"10.1016/j.neo.2025.101219","url":null,"abstract":"<div><h3>Background</h3><div>Tumor angiogenesis is essential for colorectal cancer (CRC) progression, providing oxygen and nutrients to sustain tumor growth and metastasis. Protein kinase C iota (Prkci) is an atypical protein kinase known for its oncogenic roles in various cancers; however, its function in CRC angiogenesis remains largely unexplored. This study investigates the role of Prkci in regulating tumor angiogenesis through the Jak2/Stat3 signaling pathway.</div></div><div><h3>Methods</h3><div>Prkci expression levels in CRC tissues and their correlation with micro-vessel density and patient prognosis were analyzed. Functional experiments, including endothelial cell proliferation, migration, and tube formation assays, were performed in vitro to assess the angiogenic effects of Prkci. In vivo, a CRC xenograft mouse model with Prkci knockout was used to evaluate tumor growth and angiogenesis. Mechanistic studies explored how Prkci activates Jak2 by phosphorylating it at the S633 site, leading to downstream Stat3 activation and Vegfa expression.</div></div><div><h3>Results</h3><div>Prkci was upregulated in CRC tissues and correlated with increased micro-vessel density and poor patient prognosis. In vitro, Prkci overexpression enhanced endothelial cell proliferation, migration, and tube formation, while Prkci knockout inhibited these processes. Mechanistically, Prkci phosphorylated Jak2 at S633, leading to enhanced Stat3 activation and increased Vegfa expression, which promoted angiogenesis. In vivo, Prkci knockout in CRC cells significantly reduced tumor growth, angiogenesis, and prolonged survival in a mouse model.</div></div><div><h3>Conclusions</h3><div>These findings identify Prkci as a key regulator of angiogenesis in CRC through Jak2/Stat3 signaling activation. Targeting Prkci could provide a novel therapeutic approach to inhibit tumor angiogenesis and limit CRC progression.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101219"},"PeriodicalIF":7.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879603","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

An effective multistage mouse model of esophageal carcinogenesis for preclinical and computational pathology applications 用于临床前和计算病理学应用的有效的多阶段食管癌小鼠模型

IF 7.7 2区医学

Neoplasia Pub Date : 2025-08-06 DOI: 10.1016/j.neo.2025.101217

Yuxia Fu , Guoqing Zhang , Yue Liu , Lei Xu , Yuanyuan Hu , Liyan Xue , Huiqin Guo , Yan Fu , Yigang Cen , Xiao Li , Wei Jiang , Xiying Yu

{"title":"An effective multistage mouse model of esophageal carcinogenesis for preclinical and computational pathology applications","authors":"Yuxia Fu , Guoqing Zhang , Yue Liu , Lei Xu , Yuanyuan Hu , Liyan Xue , Huiqin Guo , Yan Fu , Yigang Cen , Xiao Li , Wei Jiang , Xiying Yu","doi":"10.1016/j.neo.2025.101217","DOIUrl":"10.1016/j.neo.2025.101217","url":null,"abstract":"<div><div>The use of <em>c</em>arcinogen-<em>i</em>nduced <em>m</em>ultistage <em>c</em>arcinogenesis animal <em>m</em>odels of esophageal squamous cell carcinoma (CIMCM of ESCC) is limited by prolonged timelines, high toxicity, and excessive mutational burden. In this study, we report the establishment of an effective mouse CIMCM of ESCC by using 4-nitroquinoline-1-oxide (4NQO) as a carcinogen and sorafenib (SOR) as a tumor promoter. We show that SOR specifically activates the Raf-MEK-ERK signaling pathway in normal esophageal stratified squamous epithelium cells, thereby promoting tumor progression. This CIMCM of ESCC accurately recapitulates the multistage process of ESCC carcinogenesis from precancerous lesions to invasive carcinoma, with shortened time and high efficiency. Pathological, molecular, cellular and multiomic analyses show that the CIMCM of ESCC significantly reduces the tumor mutation burden to levels detected in human ESCC samples, while preserving key genetic driver mutations and abnormal transcriptomic/protein expression profiles. Notably, the CIMCM of ESCC demonstrates that the tissue microenvironment plays an important role in ESCC carcinogenesis, as the application of mechanical injury to the esophageal SSE of the CIMCM results in the inflammatory-related response, site-specific tumor formation and high tumor incidence. Since the CIMCM of ESCC provides valuable samples from different stages of tumor initiation and progression, the pathological whole slide images of the CIMCM of ESCC are applied to the computational pathology, which enables the detection, segmentation and annotation of the ESCC initiation and progression with pathologist-level accuracy. Taken together, this mouse CIMCM of ESCC provides a versatile platform for ESCC early diagnosis, basic and preclinical research and therapeutic strategy.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101217"},"PeriodicalIF":7.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780796","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

Disitamab vedotin combined with toripalimab and radiotherapy for multimodal organ-sparing treatment of muscle invasive bladder cancer: a proof-of-concept study 双西他单维多汀联合多利帕利单抗和放疗用于多模式器官保留治疗肌肉浸润性膀胱癌：一项概念验证研究

IF 7.7 2区医学

Neoplasia Pub Date : 2025-08-06 DOI: 10.1016/j.neo.2025.101216

Lu Zhang , Di Jin , Jingyu Zang , Lei Qian , Tianxiang Zhang , Yuchen Wu , Yu Ding , Feng Xie , Haoran Tang , Jun Xia , Dengfeng Cao , Ruiyun Zhang , Guanglei Zhuang , Haige Chen

{"title":"Disitamab vedotin combined with toripalimab and radiotherapy for multimodal organ-sparing treatment of muscle invasive bladder cancer: a proof-of-concept study","authors":"Lu Zhang , Di Jin , Jingyu Zang , Lei Qian , Tianxiang Zhang , Yuchen Wu , Yu Ding , Feng Xie , Haoran Tang , Jun Xia , Dengfeng Cao , Ruiyun Zhang , Guanglei Zhuang , Haige Chen","doi":"10.1016/j.neo.2025.101216","DOIUrl":"10.1016/j.neo.2025.101216","url":null,"abstract":"<div><h3>Purpose</h3><div>Although trimodal therapy is currently the standard organ-sparing approach for muscle-invasive bladder cancer (MIBC), its clinical benefit is limited, and noninvasive biomarkers to guide dynamic decision-making are lacking. Here, we present a proof-of-concept study evaluating disitamab vedotin (RC48, a HER2-targeted antibody-drug conjugate) combined with toripalimab (JS001, anti-PD-1) and radiotherapy for bladder preservation in localized HER2-positive MIBC.</div></div><div><h3>Patients and Methods</h3><div>In the first-stage of an open-label phase II clinical trial (ClinicalTrials.gov identifier: NCT05979740), six patients were enrolled and received disitamab vedotin, toripalimab, and radiotherapy. Adverse events were documented according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0). Tumor response was evaluated every 12 weeks by radiographic imaging, cystoscopy with biopsies, and urine cytology. In parallel, we performed longitudinal liquid biopsy analyses of circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) using PredicineCARE assay.</div></div><div><h3>Results</h3><div>The combination was overall tolerable, with no grade 4 treatment-related adverse events or deaths. Five patients (83.3 %) achieved a complete response and remained recurrence-free. Notably, utDNA testing showed high accuracy in monitoring therapeutic effectiveness and enabled early detection of tumor relapse, whereas ctDNA was largely undetectable across blood samples.</div></div><div><h3>Conclusions</h3><div>These findings establish the feasibility, efficacy, and potential biomarker utility of a novel bladder-preserving regimen, setting the stage for a paradigm shift in MIBC management.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101216"},"PeriodicalIF":7.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780795","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