NPJ Precision Oncology最新文献_第6页

Examining patient-specific responses to PARP inhibitors in a novel, human induced pluripotent stem cell-based model of breast cancer.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-25 DOI: 10.1038/s41698-025-00837-5

Carly J Weddle, Malorie Blancard, Nnamdi Uche, Praeploy Pongpamorn, Romina B Cejas, Paul W Burridge

{"title":"Examining patient-specific responses to PARP inhibitors in a novel, human induced pluripotent stem cell-based model of breast cancer.","authors":"Carly J Weddle, Malorie Blancard, Nnamdi Uche, Praeploy Pongpamorn, Romina B Cejas, Paul W Burridge","doi":"10.1038/s41698-025-00837-5","DOIUrl":"10.1038/s41698-025-00837-5","url":null,"abstract":"Preclinical models of breast cancer that better predict patient-specific drug responses are critical for expanding the clinical utility of targeted therapies, including for inhibitors of poly(ADP-ribose) polymerase (PARP). Reprogramming primary cancer cells into human induced pluripotent stem cells (hiPSCs) recently emerged as a powerful tool to model drug response phenotypes, but its use to date has been limited to hematopoietic malignancies. We designed an optimized reprogramming methodology to generate breast cancer-derived hiPSCs (BC-hiPSCs) from nine patients representing all major subtypes of breast cancer. BC-hiPSCs retain patient-specific oncogenic variants, including variants unique to individual tumor subclones. Additionally, we developed a protocol to differentiate BC-hiPSCs into mammary epithelial cells and mammary-like organoids for in vitro disease modeling, including drug response phenotyping. Using these tools, we demonstrated that BC-hiPSCs can be used to screen for differential sensitivity to PARP inhibitors and mechanistically investigated the causal genetic variant driving drug sensitivity in one patient.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"53"},"PeriodicalIF":6.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503062","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

A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-25 DOI: 10.1038/s41698-025-00816-w

Robert J Huang, Ignacio A Wichmann, Andrew Su, Anuja Sathe, Miranda V Shum, Susan M Grimes, Rithika Meka, Alison Almeda, Xiangqi Bai, Jeanne Shen, Quan Nguyen, Ingrid Luo, Summer S Han, Manuel R Amieva, Joo Ha Hwang, Hanlee P Ji

{"title":"A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors.","authors":"Robert J Huang, Ignacio A Wichmann, Andrew Su, Anuja Sathe, Miranda V Shum, Susan M Grimes, Rithika Meka, Alison Almeda, Xiangqi Bai, Jeanne Shen, Quan Nguyen, Ingrid Luo, Summer S Han, Manuel R Amieva, Joo Ha Hwang, Hanlee P Ji","doi":"10.1038/s41698-025-00816-w","DOIUrl":"10.1038/s41698-025-00816-w","url":null,"abstract":"Gastric cancer precursors demonstrate highly-variable rates of progression toward neoplasia. Certain high-risk precursors, such as gastric intestinal metaplasia with advanced histologic features, may be at up to 30-fold increased risk for progression compared to lower-risk intestinal metaplasia. The biological differences between high- and low-risk lesions have been incompletely explored. In this study, we use several clinical cohorts to characterize the microenvironment of advanced gastric cancer precursors relative to low-risk lesions using bulk, spatial, and single-cell gene expression assays. We identified a 26-gene panel which is associated with advanced lesions, localizes to metaplastic glands on histopathology, and is expressed in aberrant mature and immature intestinal cells not normally present in the healthy stomach. This gene expression signature suggests an important role of the immature intestinal lineages in promoting carcinogenesis in the metaplastic microenvironment. These findings may help to inform future biomarker development and strategies of gastric cancer prevention.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"52"},"PeriodicalIF":6.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503061","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

Pan-cancer analysis uncovered the prognostic and therapeutic value of disulfidptosis.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-24 DOI: 10.1038/s41698-025-00834-8

Yiwei Zhang, Zihua Li, Hengli Lu, Zongrui Jiang, Yixian Song, Zhanhui Ye, Chenzheng Gu, Kequan Chen, Anquan Shang

{"title":"Pan-cancer analysis uncovered the prognostic and therapeutic value of disulfidptosis.","authors":"Yiwei Zhang, Zihua Li, Hengli Lu, Zongrui Jiang, Yixian Song, Zhanhui Ye, Chenzheng Gu, Kequan Chen, Anquan Shang","doi":"10.1038/s41698-025-00834-8","DOIUrl":"10.1038/s41698-025-00834-8","url":null,"abstract":"Disulfidptosis, a newly discovered cell death mode distinct from other programmed cell death in lung and kidney cancer cells, is defined as extensive disulfide bonds to actin cytoskeleton proteins, leading to actin contraction and cytoskeletal disruption cell death. New cell death pattern discoveries often drive advances in tumor research. Therefore, the present study attempted to decipher the manifestation and importance of disulfidptosis in pan-cancer. Combining Clinical specimen immunofluorescence staining, single-cell analyses, and spatial transcriptome analyses, we demonstrated the manifestation of disulfidptosis in pan-cancer. Multi-omics analysis has revealed that genomic variants and DNA methylation in DRGs can affect the prognosis of patients with pan-cancer. The nomogram based on the DRGs Score model could accurately predict the prognosis of patients with pan-cancer. PF-562271, EHT-1864, and IPA-3 are potential therapeutic agents targeting disulfidptosis. Collectively, this study deciphered for the first time the importance of disulfidptosis for pan-cancer and developed the DRGs Score model that can assist clinicians in accurately predicting the prognosis and guiding individualized treatment of pan-cancer patients.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"50"},"PeriodicalIF":6.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492772","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

Stage-dependent spatial distribution and prognostic value of CD8⁺ tissue-resident memory T cells in NSCLC.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-22 DOI: 10.1038/s41698-025-00831-x

Liying Yang, Hao Yang, Miaoqing Zhao, Hongtu Yuan, Jiaxiao Geng, Yushan Yan, Li Wu, Ligang Xing, Jinming Yu, Xiaorong Sun

{"title":"Stage-dependent spatial distribution and prognostic value of CD8+ tissue-resident memory T cells in NSCLC.","authors":"Liying Yang, Hao Yang, Miaoqing Zhao, Hongtu Yuan, Jiaxiao Geng, Yushan Yan, Li Wu, Ligang Xing, Jinming Yu, Xiaorong Sun","doi":"10.1038/s41698-025-00831-x","DOIUrl":"10.1038/s41698-025-00831-x","url":null,"abstract":"CD8+ tissue-resident memory T cells (CD8+TRM), expressing PD-1 and/or TIM-3, are linked to immunological surveillance in non-small cell lung cancer (NSCLC). However, their prognostic value across activation states and spatial distributions in NSCLC stages is unclear. We analyzed 271 NSCLC patients' primary tumors and lymph nodes, using multiplex immunohistochemistry and inForm software for cell identification. Statistical analyses included the Mann-Whitney U test and Cox survival analysis. Findings showed CD8+TRM were categorized into four activation states. In locally advanced NSCLC, PD-1-TIM-3+CD8+TRM3, and PD-1+TIM-3+CD8+TRM4 densities were notably higher at invasive margins. Fewer interactions between CD8+TRM and tumor cells were observed in advanced lesions. Decreased PD-1+TIM-3-CD8+TRM2 interactions with tumor cells and increased PD-1+TIM-3+CD8+TRM4 interactions with tumor cells were independently associated with recurrence in patients with early lung adenocarcinoma and squamous carcinoma, respectively. These results suggest that CD8+TRM activation state and distribution are linked to recurrence risk in early-stage NSCLC, emphasizing the importance of CD8+TRM spatial dynamics in prognosis.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"51"},"PeriodicalIF":6.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476784","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

Relapse-free survival in a pediatric patient with recurrent EZH2-mutant melanoma treated with adjuvant tazemetostat. 一名接受他昔莫司他辅助治疗的复发性EZH2突变黑色素瘤儿科患者的无复发生存率。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-21 DOI: 10.1038/s41698-025-00826-8

Erin E Resch, Stavriani C Makri, Paola Ghanem, Ezra G Baraban, Kenneth J Cohen, Alan R Cohen, Evan J Lipson, Christine A Pratilas

引用次数: 0

Personalized dose selection platform for patients with solid tumors in the PRECISE CURATE.AI feasibility trial.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-21 DOI: 10.1038/s41698-025-00835-7

Agata Blasiak, Anh T L Truong, Nigel Foo, Lester W J Tan, Kirthika S Kumar, Shi-Bei Tan, Chong Boon Teo, Benjamin K J Tan, Xavier Tadeo, Hon Lyn Tan, Cheng Ean Chee, Wei Peng Yong, Dean Ho, Raghav Sundar

{"title":"Personalized dose selection platform for patients with solid tumors in the PRECISE CURATE.AI feasibility trial.","authors":"Agata Blasiak, Anh T L Truong, Nigel Foo, Lester W J Tan, Kirthika S Kumar, Shi-Bei Tan, Chong Boon Teo, Benjamin K J Tan, Xavier Tadeo, Hon Lyn Tan, Cheng Ean Chee, Wei Peng Yong, Dean Ho, Raghav Sundar","doi":"10.1038/s41698-025-00835-7","DOIUrl":"10.1038/s41698-025-00835-7","url":null,"abstract":"In oncology, the conventional reliance on the maximum tolerated dose (MTD) strategy for chemotherapy may not optimize treatment outcomes for individual patients. CURATE.AI is an AI-derived platform that utilizes a patient's own, small dataset to dynamically personalize only their own dose recommendations. The primary objective of this feasibility trial was to assess the logistical and scientific feasibility of providing dynamically personalized AI-derived chemotherapy dose recommendations for patients with advanced solid tumors at/for treatment with single-agent capecitabine, capecitabine in combination with oxaliplatin (XELOX), or capecitabine in combination with irinotecan (XELIRI). CURATE.AI demonstrated adaptability to clinically relevant situations encountered by patients often treated with palliative intent of care. High rates of user adherence were demonstrated, which could be in part due to the high engagement of the physicians in selecting data and boundaries for CURATE.AI operations.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"49"},"PeriodicalIF":6.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472750","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

Opportunities and challenges for patient-derived models of brain tumors in functional precision medicine.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-14 DOI: 10.1038/s41698-025-00832-w

Breanna Mann, Nichole Artz, Rami Darawsheh, David E Kram, Shawn Hingtgen, Andrew B Satterlee

引用次数: 0

Towards an interpretable deep learning model of cancer.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-14 DOI: 10.1038/s41698-025-00822-y

Avlant Nilsson, Nikolaos Meimetis, Douglas A Lauffenburger

引用次数: 0

Author Correction: An automated deep learning pipeline for EMVI classification and response prediction of rectal cancer using baseline MRI: a multi-centre study.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-12 DOI: 10.1038/s41698-025-00827-7

Lishan Cai, Doenja M J Lambregts, Geerard L Beets, Monique Maas, Eduardo H P Pooch, Corentin Guérendel, Regina G H Beets-Tan, Sean Benson

引用次数: 0

An integrated perspective on single-cell and spatial transcriptomic signatures in high-grade gliomas.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-11 DOI: 10.1038/s41698-025-00830-y

Célia Lemoine, Marc-Antoine Da Veiga, Bernard Rogister, Caroline Piette, Virginie Neirinckx

{"title":"An integrated perspective on single-cell and spatial transcriptomic signatures in high-grade gliomas.","authors":"Célia Lemoine, Marc-Antoine Da Veiga, Bernard Rogister, Caroline Piette, Virginie Neirinckx","doi":"10.1038/s41698-025-00830-y","DOIUrl":"10.1038/s41698-025-00830-y","url":null,"abstract":"High-grade gliomas (HGG) are incurable brain malignancies in children and adults. Breakthrough advances in transcriptomic technologies unveiled the intricate diversity of cellular states and their spatial organization within HGGs. We qualitatively integrated 55 neoplastic transcriptomic signatures described in 17 single-cell and spatial RNA sequencing-based studies. Our review delineates a spectrum of cellular states, represented by the expression of specific genes, which can be conceptualized along a \"reactive-developmental programs\" axis. Additionally, we discussed the potential cues influencing these cellular states, including how spatial organization may impact transcriptomic dynamics. Leveraging these insightful discoveries, we discussed a novel, evolutive way to integrate the different transcriptomic signatures in two or three dimensions, incorporating developmental states, their proliferative capacity, and their possible transition towards reactive states. This integrated analysis illuminates the diverse cellular landscape of HGGs and provides a valuable resource for further elucidation of malignant mechanisms, and for the design of therapeutic endeavors.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"44"},"PeriodicalIF":6.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399733","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