NPJ Precision Oncology最新文献_第3页

Assessment of targets of antibody drug conjugates in SCLC. 抗体药物偶联物在SCLC中的靶标评估。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-02 DOI: 10.1038/s41698-024-00784-7

Abhishek Ajay, Han Wang, Ali Rezvani, Omid Savari, Brandon J Grubb, Karen S McColl, Suzy Yoon, Peronne L Joseph, Shelby R Kopp, Adam M Kresak, Craig D Peacock, Gary M Wildey, Minh Lam, Masaru Miyagi, Hung-Ying Kao, Afshin Dowlati

{"title":"Assessment of targets of antibody drug conjugates in SCLC.","authors":"Abhishek Ajay, Han Wang, Ali Rezvani, Omid Savari, Brandon J Grubb, Karen S McColl, Suzy Yoon, Peronne L Joseph, Shelby R Kopp, Adam M Kresak, Craig D Peacock, Gary M Wildey, Minh Lam, Masaru Miyagi, Hung-Ying Kao, Afshin Dowlati","doi":"10.1038/s41698-024-00784-7","DOIUrl":"10.1038/s41698-024-00784-7","url":null,"abstract":"<p><p>Antibody-drug conjugate (ADC) therapy has transformed treatment for several solid tumors, including small cell lung cancer (SCLC). However, significant challenges remain, including systemic toxicity, acquired resistance, and the lack of reliable biomarkers for patient selection. To enhance the effectiveness of ADC therapies in SCLC, we focused on target selection in this study by investigating the expression of ADC targets - SEZ6, DLL3, CD276, and TACSTD2 - in cell lines and patient samples. SEZ6 expression was significantly elevated in various SCLC transcriptional subtypes, particularly ASCL1, and exhibited gender-specific differences, being lower in women. DLL3 was primarily observed in the ASCL1 subtype, while CD276 showed high expression in non-neuroendocrine subtypes. TACSTD2 levels were generally low and attenuated in lymph nodes and brain metastases compared to primary tumors. Our findings underscore the importance of understanding target expression patterns to optimize ADC therapy and advance precision medicine in SCLC treatment.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"1"},"PeriodicalIF":6.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922371","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

Genomic scarring score predicts the response to PARP inhibitors in non-small cell lung cancer 基因组疤痕评分预测非小细胞肺癌患者对PARP抑制剂的反应

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-26 DOI: 10.1038/s41698-024-00777-6

Katerina Tsilingiri, Anna Chalari, Georgia Christopoulou, Alexandra Voutsina, Pantelis Constantoulakis, Κonstantinos Potaris, Ioannis Vamvakaris, Dora Hatzidaki, Georgina Zachou, Giannis Vatsellas, Vassilis Georgoulias, Athanasios Kotsakis, Apostolos Klinakis

{"title":"Genomic scarring score predicts the response to PARP inhibitors in non-small cell lung cancer","authors":"Katerina Tsilingiri, Anna Chalari, Georgia Christopoulou, Alexandra Voutsina, Pantelis Constantoulakis, Κonstantinos Potaris, Ioannis Vamvakaris, Dora Hatzidaki, Georgina Zachou, Giannis Vatsellas, Vassilis Georgoulias, Athanasios Kotsakis, Apostolos Klinakis","doi":"10.1038/s41698-024-00777-6","DOIUrl":"10.1038/s41698-024-00777-6","url":null,"abstract":"PARP inhibitors (PARPi) have shown efficacy in tumours harbouring mutations in homologous recombination repair (HRR) genes. Somatic HRR mutations have been described in patients with Non-Small Cell Lung Cancer (NSCLC), but PARP inhibitors (PARPi) are not yet a therapeutic option. Here we assessed the homologous recombination status of early-stage NSCLC and explored the therapeutic benefit of PARPi in preclinical models. The Genomic Scarring Score GSS (GSS) and HRR mutation profile of 136 patients were assessed. High GSS (h-GSS) was observed in 39 (28.7%) patients half of which carried pathogenic/likely pathogenic somatic HRR mutations. TP53 mutations were significantly enriched in h-GSS tumours (p < 0.001). Olaparib significantly delayed tumour growth in h-GSS but not l-GSS Patient-derived Xenografts (PDXs), while patients with h-GSS/TP53mut tumours respond favourably to adjuvant platinum-based chemotherapy. Our functional data clearly support the idea that the use of GSS rather than the mutational status of HRR genes could select patients for administration of PARPi.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-11"},"PeriodicalIF":6.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00777-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890104","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

Novel radiogenomics approach to predict and characterize pneumonitis in stage III NSCLC 新的放射基因组学方法预测和表征III期非小细胞肺癌的肺炎

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-24 DOI: 10.1038/s41698-024-00790-9

Lukas Delasos, Mohammadhadi Khorrami, Vidya S. Viswanathan, Khalid Jazieh, Yifu Ding, Pushkar Mutha, Kevin Stephans, Amit Gupta, Nathan A. Pennell, Pradnya D. Patil, Kristin Higgins, Anant Madabhushi

{"title":"Novel radiogenomics approach to predict and characterize pneumonitis in stage III NSCLC","authors":"Lukas Delasos, Mohammadhadi Khorrami, Vidya S. Viswanathan, Khalid Jazieh, Yifu Ding, Pushkar Mutha, Kevin Stephans, Amit Gupta, Nathan A. Pennell, Pradnya D. Patil, Kristin Higgins, Anant Madabhushi","doi":"10.1038/s41698-024-00790-9","DOIUrl":"10.1038/s41698-024-00790-9","url":null,"abstract":"Unresectable stage III NSCLC is now treated with chemoradiation (CRT) followed by immune checkpoint inhibitors (ICI). Pneumonitis, a common CRT complication, has heightened risk with ICI, potentially causing severe outcomes. Currently, there are no biomarkers to predict pneumonitis risk or differentiate between radiation-induced pneumonitis (RTP) and ICI-induced pneumonitis (IIP). This study analyzed 293 patients from two institutions, with 140 experiencing pneumonitis (RTP: 84, IIP: 56). Two models were developed: M1 predicted pneumonitis risk using seven radiomic features, achieving high accuracy across internal and external datasets (AUCs: 0.76 and 0.85). M2 differentiated RTP from IIP, with strong performance (AUCs: 0.86 and 0.81). Gene set enrichment analysis linked high pneumonitis risk to pathways such as ECM-receptor interaction and T-cell signaling, while high IIP risk correlated with MAPK and JAK–STAT pathways. Radiomic models show promise in early pneumonitis risk stratification and distinguishing pneumonitis types, potentially guiding personalized NSCLC treatment.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-12"},"PeriodicalIF":6.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00790-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880568","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

AI-driven eyelid tumor classification in ocular oncology using proteomic data 基于蛋白质组学数据的人工智能驱动眼睑肿瘤分类

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-23 DOI: 10.1038/s41698-024-00767-8

Linyan Wang, Xizhe Dai, Zicheng Liu, Yaxing Zhao, Yaoting Sun, Bangxun Mao, Shuohan Wu, Tiansheng Zhu, Fengbo Huang, Nuliqiman Maimaiti, Xue Cai, Stan Z. Li, Jianpeng Sheng, Tiannan Guo, Juan Ye

{"title":"AI-driven eyelid tumor classification in ocular oncology using proteomic data","authors":"Linyan Wang, Xizhe Dai, Zicheng Liu, Yaxing Zhao, Yaoting Sun, Bangxun Mao, Shuohan Wu, Tiansheng Zhu, Fengbo Huang, Nuliqiman Maimaiti, Xue Cai, Stan Z. Li, Jianpeng Sheng, Tiannan Guo, Juan Ye","doi":"10.1038/s41698-024-00767-8","DOIUrl":"10.1038/s41698-024-00767-8","url":null,"abstract":"Eyelid tumors pose diagnostic challenges due to their diverse pathological types and limited biopsy materials. This study aimed to develop an artificial intelligence (AI) diagnostic system for accurate classification of eyelid tumors. Utilizing mass spectrometry-based proteomics, we analyzed proteomic data from eight tissue types and identified eighteen novel biomarkers based on 233 formalin-fixed, paraffin-embedded (FFPE) samples from 150 patients. The 18-protein model, validated by an independent cohort (99 samples from 60 patients), exhibited high accuracy (84.8%), precision (86.2%), and recall (84.8%) in multi-class classification. The model demonstrated distinct clustering of different lesion types, as visualized through UMAP plots. Receiver operator characteristic (ROC) curve analysis revealed strong predictive ability with area under the curve (AUC) values ranging from 0.80 to 1.00. This AI-based diagnostic system holds promise for improving the efficiency and precision of eyelid tumor diagnosis, addressing the limitations of traditional pathological methods.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-11"},"PeriodicalIF":6.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00767-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880581","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

Mutational disparities in colorectal cancers of White Americans, Alabama African Americans, And Oklahoma American Indians 美国白人、阿拉巴马州非裔美国人和俄克拉何马州印第安人结直肠癌的突变差异

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-23 DOI: 10.1038/s41698-024-00782-9

Hiroshi Y. Yamada, Madhusmita Rout, Chao Xu, Philip H. O’Neill, Farrukh Afaq, Katherine T. Morris, Dharambir K. Sanghera, Upender Manne, Chinthalapally V. Rao

{"title":"Mutational disparities in colorectal cancers of White Americans, Alabama African Americans, And Oklahoma American Indians","authors":"Hiroshi Y. Yamada, Madhusmita Rout, Chao Xu, Philip H. O’Neill, Farrukh Afaq, Katherine T. Morris, Dharambir K. Sanghera, Upender Manne, Chinthalapally V. Rao","doi":"10.1038/s41698-024-00782-9","DOIUrl":"10.1038/s41698-024-00782-9","url":null,"abstract":"The high incidence and mortality rates of colorectal cancer (CRC) in Alabama African Americans (AAs) and Oklahoma American Indians (AIs) are recognized as cancer disparities, yet the underlying causes have been poorly demonstrated. By evaluating CRC whole-exome sequencing and mutational profiles, here we report sets of mutated genes whose frequencies differed significantly (p < 0.05) in a race-specific manner. Secondary screening with cancer database identified “survival-critical genes (SCGs)” (i.e., genes whose mutations/alterations are associated with significant differences in the patients’ survival rates) among the differentially mutated genes. Notable SCGs with race-pronounced variants were different from DEGs and their involved pathways included nucleotide catabolism and cell cycle checkpoints for AAs, and extracellular matrix organization for AIs. The inclusion of these SCGs with race-pronounced variants in the clinical CRC next-generation sequencing panels and the development of targeting drugs will serve as refinements for precision medicine to overcome racial disparities in health outcomes of CRC.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-14"},"PeriodicalIF":6.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00782-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880555","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

Deep learning for endometrial cancer subtyping and predicting tumor mutational burden from histopathological slides 深度学习用于子宫内膜癌亚型分型和从组织病理切片预测肿瘤突变负担。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-21 DOI: 10.1038/s41698-024-00766-9

Ching-Wei Wang, Nabila Puspita Firdi, Yu-Ching Lee, Tzu-Chiao Chu, Hikam Muzakky, Tzu-Chien Liu, Po-Jen Lai, Tai-Kuang Chao

{"title":"Deep learning for endometrial cancer subtyping and predicting tumor mutational burden from histopathological slides","authors":"Ching-Wei Wang, Nabila Puspita Firdi, Yu-Ching Lee, Tzu-Chiao Chu, Hikam Muzakky, Tzu-Chien Liu, Po-Jen Lai, Tai-Kuang Chao","doi":"10.1038/s41698-024-00766-9","DOIUrl":"10.1038/s41698-024-00766-9","url":null,"abstract":"Endometrial cancer (EC) diagnosis traditionally relies on tumor morphology and nuclear grade, but personalized therapy demands a deeper understanding of tumor mutational burden (TMB), i.e., a key biomarker for immune checkpoint inhibition and immunotherapy response. Traditional TMB prediction methods, such as sequencing exomes or whole genomes, are costly and often unavailable in clinical settings. We present the first TR-MAMIL deep learning framework to predict TMB status and classify the EC cancer subtype directly from H&E-stained WSIs, enabling effective personalized immunotherapy planning and prognostic refinement of EC patients. Our models were evaluated on a large dataset from The Cancer Genome Atlas. TR-MAMIL performed exceptionally well in classifying aggressive and non-aggressive EC, as well as predicting TMB, outperforming seven state-of-the-art approaches. It also performed well in classifying normal and abnormal p53 mutations in EC using H&E WSIs. Kaplan–Meier analysis further demonstrated TR-MAMIL’s ability to differentiate patients with longer survival in the aggressive EC.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-18"},"PeriodicalIF":6.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00766-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872043","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

Breast cancer brain metastases genomic profiling identifies alterations targetable by immune-checkpoint and PARP inhibitors 乳腺癌脑转移的基因组分析鉴定免疫检查点和PARP抑制剂可靶向的改变。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-20 DOI: 10.1038/s41698-024-00761-0

A. Giannoudis, E. S. Sokol, T. Bhogal, S. H. Ramkissoon, E. D. Razis, R. Bartsch, J. A. Shaw, K. McGregor, Alison Clark, R.S.P. Huang, C. Palmieri

{"title":"Breast cancer brain metastases genomic profiling identifies alterations targetable by immune-checkpoint and PARP inhibitors","authors":"A. Giannoudis, E. S. Sokol, T. Bhogal, S. H. Ramkissoon, E. D. Razis, R. Bartsch, J. A. Shaw, K. McGregor, Alison Clark, R.S.P. Huang, C. Palmieri","doi":"10.1038/s41698-024-00761-0","DOIUrl":"10.1038/s41698-024-00761-0","url":null,"abstract":"Understanding the genomic landscape of breast cancer brain metastases (BCBMs) is key to developing targeted treatments. In this study, targetable genomic profiling was performed on 822 BCBMs, 11,988 local breast cancer (BC) biopsies and 15,516 non-central nervous system (N-CNS) metastases (all unpaired samples) collected during the course of routine clinical care by Foundation Medicine Inc (Boston, MA). Clinically relevant genomic alterations were significantly enriched in BCBMs compared to local BCs and N-CNS metastases. Homologous recombination deficiency as measured by BRCA1/2 alteration prevalence and loss-of-heterozygosity and immune checkpoint inhibitor (ICI) biomarkers [Tumor mutation burden (TMB)-High, Microsatellite instability (MSI)-High, PD-L1/L2)] were significantly more prevalent in BCBM than local BC and N-CNS. High PD-L1 protein expression was observed in ER-negative/HER2-negative BCBMs (48.3% vs 50.0% in local BCs, 21.4% in N-CNS). Our data highlights that a high proportion of BCBMs are potentially amenable to treatment with targeted therapeutic agents including PARP inhibitors and ICIs.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-11"},"PeriodicalIF":6.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00761-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872686","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

HuR inhibition overcomes cFLIP-mediated doxorubicin resistance in triple-negative breast cancer 在三阴性乳腺癌中，HuR抑制克服了cdna介导的阿霉素耐药。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-20 DOI: 10.1038/s41698-024-00780-x

Lanjing Wei, Sung Hae Kim, Ahlam M. Armaly, Jeffrey Aubé, Liang Xu, Xiaoqing Wu

{"title":"HuR inhibition overcomes cFLIP-mediated doxorubicin resistance in triple-negative breast cancer","authors":"Lanjing Wei, Sung Hae Kim, Ahlam M. Armaly, Jeffrey Aubé, Liang Xu, Xiaoqing Wu","doi":"10.1038/s41698-024-00780-x","DOIUrl":"10.1038/s41698-024-00780-x","url":null,"abstract":"Triple-negative breast cancer (TNBC) presents therapeutic challenges due to limited targeted treatment options and resistance to chemotherapy drugs, such as doxorubicin. This study investigated doxorubicin resistance mechanisms and a strategy to overcome it. A doxorubicin-resistant cell subline (231-DR) was developed from MDA-MB-231 TNBC cells, and enhanced expression of cellular FLICE-inhibitory protein (cFLIP) in 231-DR cells was identified as a potential driver of the resistance. Overexpression of cFLIP conferred resistance to doxorubicin-induced apoptosis, whereas siRNA-mediated cFLIP depletion induced apoptosis, particularly in 231-DR cells. Furthermore, the RNA-binding protein Hu antigen R (HuR) was found to regulate cFLIP expression. HuR Inhibition with KH-3 or RNA interference reduced cFLIP levels. Importantly, KH-3 sensitized TNBC cells to doxorubicin-induced apoptosis. In summary, this study delineates cFLIP’s role in mediating doxorubicin resistance and identifies HuR as a positive regulator of cFLIP, offering a novel therapeutic avenue against chemoresistance in TNBC by combining HuR inhibition with doxorubicin.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-12"},"PeriodicalIF":6.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00780-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872361","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

ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells ACSL3在胆管癌患者中是一个不利的预后标志物，并赋予胆管癌细胞对铁下垂的抗性。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-20 DOI: 10.1038/s41698-024-00783-8

Apiwit Sae-Fung, Nawaporn Vinayavekhin, Bengt Fadeel, Siriporn Jitkaew

{"title":"ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells","authors":"Apiwit Sae-Fung, Nawaporn Vinayavekhin, Bengt Fadeel, Siriporn Jitkaew","doi":"10.1038/s41698-024-00783-8","DOIUrl":"10.1038/s41698-024-00783-8","url":null,"abstract":"Cholangiocarcinoma (CCA) is a bile duct malignancy. Our previous comprehensive analysis showed that ferroptosis-related genes can stratify CCA patients into low-risk and high-risk groups based on survival time. Here, we explored the role of ferroptosis in CCA by analyzing mRNA expression in CCA patients from public databases. We identified acyl-CoA synthetase long chain family member 3 (ACSL3) as a potential ferroptosis suppressor in high-risk CCA patients. Using a panel of CCA cell lines, we confirmed ACSL3 upregulation in CCA cell lines associated with high-risk CCA, correlating this with resistance to the ferroptosis inducer RSL3. Lipidomic analysis revealed increased monounsaturated fatty acid (MUFA)-containing phospholipids in resistant cell lines. ACSL3 silencing sensitized these cells to RSL3. Resistance to ferroptosis was also dependent on exogenous MUFAs and was enhanced by lipid droplet biogenesis inhibition. These findings highlight ACSL3 as a promising target for therapeutic strategies aimed at overcoming ferroptosis resistance in CCA.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-14"},"PeriodicalIF":6.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00783-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872684","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

Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer 错配修复缺陷子宫内膜癌中共享新抗原景观的特征。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2024-12-20 DOI: 10.1038/s41698-024-00779-4

Elisa De Paolis, Camilla Nero, Elisa Micarelli, Guido Leoni, Alessia Piermattei, Rita Trozzi, Elisa Scarselli, Anna Morena D’Alise, Luciano Giacò, Maria De Bonis, Alessia Preziosi, Gennaro Daniele, Diletta Piana, Tina Pasciuto, Gianfranco Zannoni, Angelo Minucci, Giovanni Scambia, Andrea Urbani, Francesco Fanfani

{"title":"Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer","authors":"Elisa De Paolis, Camilla Nero, Elisa Micarelli, Guido Leoni, Alessia Piermattei, Rita Trozzi, Elisa Scarselli, Anna Morena D’Alise, Luciano Giacò, Maria De Bonis, Alessia Preziosi, Gennaro Daniele, Diletta Piana, Tina Pasciuto, Gianfranco Zannoni, Angelo Minucci, Giovanni Scambia, Andrea Urbani, Francesco Fanfani","doi":"10.1038/s41698-024-00779-4","DOIUrl":"10.1038/s41698-024-00779-4","url":null,"abstract":"Endometrial cancer (EC) with Mismatch Repair deficiency (MMRd) is characterized by the accumulation of insertions/deletions at microsatellite sites. These mutations lead to the synthesis of frameshift peptides (FSPs) that represent tumor-specific neoantigens (nAg) proved to be shared across patients/tumors with MMRd. In this study, we explored the feasibility of a nAg-based cancer vaccination design in EC with MMRd. We adopted a whole exome sequencing approach and ad hoc bioinformatics pipelines to characterize FSPs in 35 patients with EC. A mean of 146 mutated mononucleotide repeats (MNRs) was identified with enrichment in the patients’ group with MLH1 impairment. A high coverage emerged from the comparative analysis of the EC FSPs with the content of the previously validated NOUS-209 vaccine. We obtained pieces of evidence of FSPs translation as expressed proteins from Ribo-seq, supporting the potential as the target of vaccination. The development of a nAgs-based vaccine strategy in MMRd EC may be further explored.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":" ","pages":"1-9"},"PeriodicalIF":6.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41698-024-00779-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871805","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