NPJ Precision Oncology最新文献

Immunologic correlates in a CIC::DUX4 fusion-positive sarcoma responsive to dual immune checkpoint blockade.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-25 DOI: 10.1038/s41698-025-00878-w

Olayode O Babatunde, Sara Coca Membribes, Cristina Anthonescu, Martina Bradic, Bernard O'Malley, Irina Linkov, Edmund Bartlett, Parisa Momtaz, Kaled Alektiar, Mrinal M Gounder, Evan Rosenbaum, William D Tap, Sandra P D'Angelo, Ciara M Kelly

{"title":"Immunologic correlates in a CIC::DUX4 fusion-positive sarcoma responsive to dual immune checkpoint blockade.","authors":"Olayode O Babatunde, Sara Coca Membribes, Cristina Anthonescu, Martina Bradic, Bernard O'Malley, Irina Linkov, Edmund Bartlett, Parisa Momtaz, Kaled Alektiar, Mrinal M Gounder, Evan Rosenbaum, William D Tap, Sandra P D'Angelo, Ciara M Kelly","doi":"10.1038/s41698-025-00878-w","DOIUrl":"https://doi.org/10.1038/s41698-025-00878-w","url":null,"abstract":"CIC::DUX4 sarcoma (CDS) is a rare and aggressive subtype of soft tissue sarcoma with poor prognosis and limited treatment options. Immunotherapy has not been studied in this disease. To our knowledge, response to immune checkpoint blockade (ICB) has not been previously reported. Here, we present the first case of a patient with CDS responding to dual ICB with nivolumab and relatlimab. Immunohistochemical (IHC) analysis of pre-treatment samples revealed minimal immune cell infiltration, with scarce CD3+, CD8+, and FOXP3+ T-cells and negligible expression of PD-L1 and PD-1 markers. Post-treatment tumor samples revealed a significant shift in the immune microenvironment, with increased CD8 + T-cell infiltration and co-expression of exhaustion markers PD-1 and LAG-3 following treatment. These findings suggest that doublet ICB can activate an antitumor immune response in CDS, overcoming the immune cold phenotype typically associated with this sarcoma. This case provides the first evidence of dual PD-1/LAG-3 blockade inducing an immune response in CDS. The favorable response and tolerability observed in this patient highlight the potential of dual ICB as a therapeutic option in CDS that merits further investigation.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"85"},"PeriodicalIF":6.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Circulating tumor DNA to monitor treatment response in solid tumors and advance precision oncology.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-24 DOI: 10.1038/s41698-025-00876-y

Alexandra Bartolomucci, Monyse Nobrega, Tadhg Ferrier, Kyle Dickinson, Nivedita Kaorey, Amélie Nadeau, Alberto Castillo, Julia V Burnier

引用次数: 0

Comparative analysis of RNA expression in a single institution cohort of pediatric cancer patients. 对单一机构儿科癌症患者队列中的 RNA 表达进行比较分析。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-22 DOI: 10.1038/s41698-025-00852-6

Yvonne A Vasquez, Holly C Beale, Lauren Sanders, A Geoffrey Lyle, Ellen T Kephart, Katrina Learned, Drew Thompson, Jennifer Peralez, Amy Li, Min Huang, Kimberly A Pyke-Grimm, Sofie R Salama, David Haussler, Isabel Bjork, L Spunt Sheri, Olena M Vaske

{"title":"Comparative analysis of RNA expression in a single institution cohort of pediatric cancer patients.","authors":"Yvonne A Vasquez, Holly C Beale, Lauren Sanders, A Geoffrey Lyle, Ellen T Kephart, Katrina Learned, Drew Thompson, Jennifer Peralez, Amy Li, Min Huang, Kimberly A Pyke-Grimm, Sofie R Salama, David Haussler, Isabel Bjork, L Spunt Sheri, Olena M Vaske","doi":"10.1038/s41698-025-00852-6","DOIUrl":"10.1038/s41698-025-00852-6","url":null,"abstract":"With the low incidence of mutations in pediatric cancers, alternate genomic approaches are needed to identify therapeutic targets. Our study, the Comparative Analysis of RNA Expression to Improve Pediatric and Young Adult Cancer Treatment, was conducted by the UC Santa Cruz Treehouse Childhood Cancer Initiative and Stanford University School of Medicine. RNA sequencing data from 33 children and young adults with a relapsed, refractory or rare cancer underwent CARE analysis to reveal activated cancer driver pathways and nominate treatments. We compare our pipeline to other gene expression outlier detection approaches and discuss challenges for clinical implementation. Of our 33 patients, 31 (94%) had findings of potential clinical significance. Findings were implemented in 5 patients, 3 of which had defined clinical benefit. We demonstrate that comparator cohort composition determines which outliers are detected. This study highlights the clinical utility and challenges of implementing comparative RNA sequencing analysis in the clinic.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"81"},"PeriodicalIF":6.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677109","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}

引用次数: 0

Functional combinatorial precision medicine for predicting and optimizing soft tissue sarcoma treatments.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-22 DOI: 10.1038/s41698-025-00851-7

Sharon Pei Yi Chan, Masturah Bte Mohd Abdul Rashid, Jhin Jieh Lim, Janice Jia Ni Goh, Wai Yee Wong, Lissa Hooi, Nur Nadiah Ismail, Baiwen Luo, Benjamin Jieming Chen, Nur Fazlin Bte Mohamed Noor, Brandon Xuan Ming Phua, Andre Villanueva, Xin Xiu Sam, Chin-Ann Johnny Ong, Claramae Shulyn Chia, Suraya Zainul Abidin, Ming-Hui Yong, Krishan Kumar, London Lucien Ooi, Timothy Kwang Yong Tay, Xing Yi Woo, Tan Boon Toh, Valerie Shiwen Yang, Edward Kai-Hua Chow

{"title":"Functional combinatorial precision medicine for predicting and optimizing soft tissue sarcoma treatments.","authors":"Sharon Pei Yi Chan, Masturah Bte Mohd Abdul Rashid, Jhin Jieh Lim, Janice Jia Ni Goh, Wai Yee Wong, Lissa Hooi, Nur Nadiah Ismail, Baiwen Luo, Benjamin Jieming Chen, Nur Fazlin Bte Mohamed Noor, Brandon Xuan Ming Phua, Andre Villanueva, Xin Xiu Sam, Chin-Ann Johnny Ong, Claramae Shulyn Chia, Suraya Zainul Abidin, Ming-Hui Yong, Krishan Kumar, London Lucien Ooi, Timothy Kwang Yong Tay, Xing Yi Woo, Tan Boon Toh, Valerie Shiwen Yang, Edward Kai-Hua Chow","doi":"10.1038/s41698-025-00851-7","DOIUrl":"10.1038/s41698-025-00851-7","url":null,"abstract":"Soft tissue sarcomas (STS) are rare, heterogeneous tumors with poor survival outcomes, primarily due to reliance on cytotoxic chemotherapy and lack of targeted therapies. Given the uniquely individualized nature of STS, we hypothesized that the ex vivo drug sensitivity platform, quadratic phenotypic optimization platform (QPOP), can predict treatment response and enhance combination therapy design for STS. Using QPOP, we screened 45 primary STS patient samples, and showed improved or concordant patient outcomes that are attributable to QPOP predictions. From a panel of approved and investigational agents, QPOP identified AZD5153 (BET inhibitor) and pazopanib (multi-kinase blocker) as the most effective combination with superior efficacy compared to standard regimens. Validation in a panel of established patient lines and in vivo models supported its synergistic interaction, accompanied by repressed oncogenic MYC and related pathways. These findings provide preliminary clinical evidence for QPOP to predict STS treatment outcomes and guide the development of novel therapeutic strategies for STS patients.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"83"},"PeriodicalIF":6.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692801","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}

引用次数: 0

Design of self-assembled micelles based on natural dual-targeting strategies and evaluation of their anti-liver cancer effects as drug delivery systems. 基于天然双靶向策略的自组装胶束设计及其作为药物输送系统的抗肝癌效果评估。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-22 DOI: 10.1038/s41698-025-00869-x

Binbin Wang, Bai Lv, Hao Li, Jie Zhang, Yaning Ding, Jianwen Zhou, Ming Bu, Li Fan, Cuiyan Han

{"title":"Design of self-assembled micelles based on natural dual-targeting strategies and evaluation of their anti-liver cancer effects as drug delivery systems.","authors":"Binbin Wang, Bai Lv, Hao Li, Jie Zhang, Yaning Ding, Jianwen Zhou, Ming Bu, Li Fan, Cuiyan Han","doi":"10.1038/s41698-025-00869-x","DOIUrl":"10.1038/s41698-025-00869-x","url":null,"abstract":"Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and in China, Most patients are already in an advanced stage at the time of diagnosis, and the chance of complete surgical resection is lost, therefore, drug treatment is particularly important. Angelica sinensis polysaccharide (ASP) has natural liver-targeting properties, berberine (BBR) is a lipophilic cation with anticancer activities and mitochondrial-targeting properties, and honokiol (HNK) has mitochondria-dependent anticancer effects against cancer. Therefore, the aim of the present work was to synthesize Angelica sinensis polysaccharide-berberineamphiphilic polymer (ASP-SS-BBR) loaded with HNK to prepare the micelles ASP-BBR-PM@HNK to improve the hepatic targeting ability of the nanoparticles and the mitochondrial targeting ability in HCC cells and to enhance the anti-HCC effect of HNK. The findings of this study demonstrate the successful synthesis of ASP-BBR-PM@HNK, characterized by a particle size of 48.6 ± 1.13 nm. The formulation exhibits commendable stability, a sustained-release profile, and the capability for glutathione (GSH)-responsive release. ASP-BBR-PM@HNK is efficiently internalized by HepG2 cells, exhibiting the highest rate of cell inhibition. Additionally, the use of Gal and Man as receptor blockers confirmed the formulation's superior targeting capabilities, including exceptional mitochondrial targeting. Subsequent in vivo experiments employing BALB/c nude mice as a model further corroborated these experimental outcomes. This research has successfully developed an effective natural dual-targeting system, offering a novel approach for the precise treatment of liver cancer.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"82"},"PeriodicalIF":6.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677112","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}

引用次数: 0

ARRB2 promotes cervical cancer progression via stabilizing CDC25A mRNA through m6A-IGF2BP1-dependent manner. ARRB2 通过 m6A-IGF2BP1 依赖性方式稳定 CDC25A mRNA，从而促进宫颈癌的进展。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-21 DOI: 10.1038/s41698-025-00862-4

Lijie Li, Jie Zeng, Mengying Liu, Hui Cheng, Yuyin He, Sili He, Chen Wang

{"title":"ARRB2 promotes cervical cancer progression via stabilizing CDC25A mRNA through m6A-IGF2BP1-dependent manner.","authors":"Lijie Li, Jie Zeng, Mengying Liu, Hui Cheng, Yuyin He, Sili He, Chen Wang","doi":"10.1038/s41698-025-00862-4","DOIUrl":"10.1038/s41698-025-00862-4","url":null,"abstract":"Cervical cancer causes many deaths among women worldwide. Exploring the mechanisms underlying proliferation and metastasis contributes to developing novel intervention strategies. Here, we found that ARRB2 was highly expressed, and its increased expression was associated with poor prognosis of patients with cervical cancer. Knockdown of ARRB2 repressed the proliferation, migration, invasion and EMT of cervical cancer cells. Furthermore, CDC25A was upregulated, and ARRB2 stabilized CDC25A mRNA through IGF2BP1. CDC25A silencing inhibited proliferation, migration, and invasion, but it was reversed by ARRB2 overexpression. Silencing of CDC25A suppressed EMT signaling via promoting FOXO3 phosphorylation and cytoplasmic localization and inhibiting Snail1 transcription. Knockdown of ARRB2 suppressed tumor growth and metastasis through CDC25A downregulation. In conclusion, ARRB2 promotes FOXO3 nuclear translocation and Snail1 transcription by stabilizing CDC25A mRNA in an m6A-dependent manner, thus facilitating proliferation and metastasis in cervical cancer.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"80"},"PeriodicalIF":6.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677106","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}

引用次数: 0

Multi-omics analysis identifies glioblastoma dependency on H3K9me3 methyltransferase activity.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-20 DOI: 10.1038/s41698-025-00829-5

Qiqi Xie, Yuanning Du, Sugata Ghosh, Saranya Rajendran, Aaron A Cohen-Gadol, José-Manuel Baizabal, Kenneth P Nephew, Leng Han, Jia Shen

{"title":"Multi-omics analysis identifies glioblastoma dependency on H3K9me3 methyltransferase activity.","authors":"Qiqi Xie, Yuanning Du, Sugata Ghosh, Saranya Rajendran, Aaron A Cohen-Gadol, José-Manuel Baizabal, Kenneth P Nephew, Leng Han, Jia Shen","doi":"10.1038/s41698-025-00829-5","DOIUrl":"10.1038/s41698-025-00829-5","url":null,"abstract":"Histone H3 lysine 9 dimethylation and trimethylation (H3K9me2/3) are prevalent in human genomes, especially in heterochromatin and specific euchromatic genes. Methylation of H3K9 is modulated by enzymes such as SUV39H1, SUV39H2, SETDB1, SETDB2, and EHMT1/2, which influence cancer progression. This study reveals differential expression of these six H3K9 methyltransferases in tumors, with SUV39H1, SUV39H2, and SETDB1 showing significant links to cancer phenotypes. We developed the \"H3K9me3 MtSig\" (H3K9me3 methyltransferases signature) based on these findings. H3K9me3 MtSig is unique to various tumors, with prognostic significance and associations with key signaling pathways, especially in glioblastoma (GBM). Elevated H3K9me3 MtSig was observed in GBM samples, correlating with the G2/M cell cycle and reduced immune responses. H3K9me3-mediated repetitive sequence silencing by H3K9me3 MtSig contributed to these phenotypes, and inhibiting H3K9me3 MtSig in patient-derived GBM cells suppressed proliferation and increased immune responses. H3K9me3 MtSig serves as an independent prognostic factor and potential therapeutic target.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"78"},"PeriodicalIF":6.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670441","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}

引用次数: 0

Real-time image fusion and Apple Vision Pro in laparoscopic microwave ablation of hepatic hemangiomas.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-20 DOI: 10.1038/s41698-025-00867-z

Tao Lan, Sichun Liu, Yihe Dai, Jia Luo, Jiang Han, Yun Jin

{"title":"Real-time image fusion and Apple Vision Pro in laparoscopic microwave ablation of hepatic hemangiomas.","authors":"Tao Lan, Sichun Liu, Yihe Dai, Jia Luo, Jiang Han, Yun Jin","doi":"10.1038/s41698-025-00867-z","DOIUrl":"10.1038/s41698-025-00867-z","url":null,"abstract":"Laparoscopic ultrasound-guided liver microwave ablation requires precise navigation and spatial accuracy. We developed an image fusion navigation system that integrates laparoscopic, ultrasound, and 3D liver model images into a unified real-time visualization. The Apple Vision Pro mixed reality device projects all essential image information into the surgeon's field of view in real-time. This system reduces cognitive load and enhances surgical precision and efficiency. Comparative experiments showed a significant improvement in puncture accuracy under AVP guidance (success rate of 90%) compared to traditional methods (42.5%), benefiting both novice and experienced surgeons. According to the NASA Task Load Index evaluation, the system also reduced the workload of surgeons. In eight patients, ablation was successful with minimal blood loss, no major complications, and rapid recovery. Despite challenges such as cost and fatigue, these results highlight the potential of mixed reality technology to improve spatial navigation, reduce cognitive demands, and optimize complex surgical procedures.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"79"},"PeriodicalIF":6.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670443","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}

引用次数: 0

Prediction and analysis of tumor infiltrating lymphocytes across 28 cancers by TILScout using deep learning.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-19 DOI: 10.1038/s41698-025-00866-0

Huibo Zhang, Lulu Chen, Lan Li, Yang Liu, Barnali Das, Shuang Zhai, Juan Tan, Yan Jiang, Simona Turco, Yi Yao, Dmitrij Frishman

{"title":"Prediction and analysis of tumor infiltrating lymphocytes across 28 cancers by TILScout using deep learning.","authors":"Huibo Zhang, Lulu Chen, Lan Li, Yang Liu, Barnali Das, Shuang Zhai, Juan Tan, Yan Jiang, Simona Turco, Yi Yao, Dmitrij Frishman","doi":"10.1038/s41698-025-00866-0","DOIUrl":"10.1038/s41698-025-00866-0","url":null,"abstract":"The density of tumor-infiltrating lymphocytes (TILs) serves as a valuable indicator for predicting anti-tumor responses, but its broad impact across various types of cancers remains underexplored. We introduce TILScout, a pan-cancer deep-learning approach to compute patch-level TIL scores from whole slide images (WSIs). TILScout achieved accuracies of 0.9787 and 0.9628, and AUCs of 0.9988 and 0.9934 in classifying WSI patches into three categories-TIL-positive, TIL-negative, and other/necrotic-on validation and independent test sets, respectively, surpassing previous studies. The biological significance of TILScout-derived TIL scores across 28 cancers was validated through comprehensive functional and correlational analyses. A consistent decrease in TIL scores with an increase in cancer stage provides direct evidence that the lower TIL content may stimulate cancer progression. Additionally, TIL scores correlated with immune checkpoint gene expression and genomic variation in common cancer driver genes. Our comprehensive pan-cancer survey highlights the critical prognostic significance of TILs within the tumor microenvironment.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"76"},"PeriodicalIF":6.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664083","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}

引用次数: 0

Revealing neuroendocrine transformation in gynecological cancers through genomic analysis.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-19 DOI: 10.1038/s41698-025-00861-5

Ann Oluloro, David L Wells, Charles K Childers, Tiffany Luu, Keith D Eaton, Renata R Urban, Eric Q Konnick, Vera A Paulson, Kalyan Banda

{"title":"Revealing neuroendocrine transformation in gynecological cancers through genomic analysis.","authors":"Ann Oluloro, David L Wells, Charles K Childers, Tiffany Luu, Keith D Eaton, Renata R Urban, Eric Q Konnick, Vera A Paulson, Kalyan Banda","doi":"10.1038/s41698-025-00861-5","DOIUrl":"10.1038/s41698-025-00861-5","url":null,"abstract":"Neuroendocrine transformation (NT) in cancers, typically observed under the selective pressure of targeted therapies, involves lineage plasticity where adenocarcinomas adopt neuroendocrine characteristics while retaining the molecular alterations of their original histology. This phenomenon, well-documented in prostate and lung cancers, has not been observed in gynecological malignancies until now. We present two pivotal cases involving primary ovarian and uterine cancers that developed neuroendocrine carcinomas post-treatment. Initially presumed to be independent primaries, comprehensive next-generation sequencing technologies, including UW-OncoPlex and BROCA panels, were used to establish a clonal relationship between the primary tumors and their respective neuroendocrine metastases. This report provides the first documented instances of NT in gynecological cancers, indicating that it may be a more widespread resistance mechanism than previously recognized. Routine re-biopsy and early integration of advanced molecular diagnostics into clinical practice will identify NT and provide insights into pathogenesis and eventual therapeutic options.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"77"},"PeriodicalIF":6.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664085","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}

引用次数: 0