NAR cancer最新文献_第6页

A large-scale study of peptide features defining immunogenicity of cancer neo-epitopes. 对确定癌症新表位免疫原性的多肽特征进行大规模研究。

IF 3.4

NAR cancer Pub Date : 2024-01-29 eCollection Date: 2024-03-01 DOI: 10.1093/narcan/zcae002

Yat-Tsai Richie Wan, Zeynep Koşaloğlu-Yalçın, Bjoern Peters, Morten Nielsen

{"title":"A large-scale study of peptide features defining immunogenicity of cancer neo-epitopes.","authors":"Yat-Tsai Richie Wan, Zeynep Koşaloğlu-Yalçın, Bjoern Peters, Morten Nielsen","doi":"10.1093/narcan/zcae002","DOIUrl":"10.1093/narcan/zcae002","url":null,"abstract":"Accurate prediction of immunogenicity for neo-epitopes arising from a cancer associated mutation is a crucial step in many bioinformatics pipelines that predict outcome of checkpoint blockade treatments or that aim to design personalised cancer immunotherapies and vaccines. In this study, we performed a comprehensive analysis of peptide features relevant for prediction of immunogenicity using the Cancer Epitope Database and Analysis Resource (CEDAR), a curated database of cancer epitopes with experimentally validated immunogenicity annotations from peer-reviewed publications. The developed model, ICERFIRE (ICore-based Ensemble Random Forest for neo-epitope Immunogenicity pREdiction), extracts the predicted ICORE from the full neo-epitope as input, i.e. the nested peptide with the highest predicted major histocompatibility complex (MHC) binding potential combined with its predicted likelihood of antigen presentation (%Rank). Key additional features integrated into the model include assessment of the BLOSUM mutation score of the neo-epitope, and antigen expression levels of the wild-type counterpart which is often reflecting a neo-epitope's abundance. We demonstrate improved and robust performance of ICERFIRE over existing immunogenicity and epitope prediction models, both in cross-validation and on external validation datasets.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"6 1","pages":"zcae002"},"PeriodicalIF":3.4,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The ORFIUS complex regulates ORC2 localization at replication origins. ORFIUS 复合物调节 ORC2 在复制起源的定位。

IF 3.4

NAR cancer Pub Date : 2024-01-29 eCollection Date: 2024-03-01 DOI: 10.1093/narcan/zcae003

Zelei Yang, Saie Mogre, Ruiyang He, Emma L Berdan, Shannan J Ho Sui, Sarah J Hill

{"title":"The ORFIUS complex regulates ORC2 localization at replication origins.","authors":"Zelei Yang, Saie Mogre, Ruiyang He, Emma L Berdan, Shannan J Ho Sui, Sarah J Hill","doi":"10.1093/narcan/zcae003","DOIUrl":"10.1093/narcan/zcae003","url":null,"abstract":"High-grade serous ovarian cancer (HGSC) is a lethal malignancy with elevated replication stress (RS) levels and defective RS and RS-associated DNA damage responses. Here we demonstrate that the bromodomain-containing protein BRD1 is a RS suppressing protein that forms a replication origin regulatory complex with the histone acetyltransferase HBO1, the BRCA1 tumor suppressor, and BARD1, ORigin FIring Under Stress (ORFIUS). BRD1 and HBO1 promote eventual origin firing by supporting localization of the origin licensing protein ORC2 at origins. In the absence of BRD1 and/or HBO1, both origin firing and nuclei with ORC2 foci are reduced. BRCA1 regulates BRD1, HBO1, and ORC2 localization at replication origins. In the absence of BRCA1, both origin firing and nuclei with BRD1, HBO1, and ORC2 foci are increased. In normal and non-HGSC ovarian cancer cells, the ORFIUS complex responds to ATR and CDC7 origin regulatory signaling and disengages from origins during RS. In BRCA1-mutant and sporadic HGSC cells, BRD1, HBO1, and ORC2 remain associated with replication origins, and unresponsive to RS, DNA damage, or origin regulatory kinase inhibition. ORFIUS complex dysregulation may promote HGSC cell survival by allowing for upregulated origin firing and cell cycle progression despite accumulating DNA damage, and may be a RS target.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"6 1","pages":"zcae003"},"PeriodicalIF":3.4,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to 'Translation reprogramming by eIF3 linked to glioblastoma resistance'. eIF3 的翻译重编程与胶质母细胞瘤的抗药性有关 "的更正。

IF 3.4

NAR cancer Pub Date : 2024-01-15 eCollection Date: 2024-03-01 DOI: 10.1093/narcan/zcae001

引用次数: 0

Single-cell genomics analysis reveals complex genetic interactions in an in vivo model of acquired BRAF inhibitor resistance. 单细胞基因组学分析揭示了获得性 BRAF 抑制剂耐药性体内模型中复杂的基因相互作用。

IF 3.4

NAR cancer Pub Date : 2024-01-11 eCollection Date: 2024-03-01 DOI: 10.1093/narcan/zcad061

Jacob L Schillo, Charlotte R Feddersen, Rebekah M Peplinski, Lexy S Powell, Afshin Varzavand, Christopher S Stipp, Jesse D Riordan, Adam J Dupuy

{"title":"Single-cell genomics analysis reveals complex genetic interactions in an in vivo model of acquired BRAF inhibitor resistance.","authors":"Jacob L Schillo, Charlotte R Feddersen, Rebekah M Peplinski, Lexy S Powell, Afshin Varzavand, Christopher S Stipp, Jesse D Riordan, Adam J Dupuy","doi":"10.1093/narcan/zcad061","DOIUrl":"10.1093/narcan/zcad061","url":null,"abstract":"The evolution of therapeutic resistance is a major obstacle to the success of targeted oncology drugs. While both inter- and intratumoral heterogeneity limit our ability to detect resistant subpopulations that pre-exist or emerge during treatment, our ability to analyze tumors with single-cell resolution is limited. Here, we utilized a cell-based transposon mutagenesis method to identify mechanisms of BRAF inhibitor resistance in a model of cutaneous melanoma. This screen identified overexpression of NEDD4L and VGLL3 as significant drivers of BRAF inhibitor resistance in vivo. In addition, we describe a novel single-cell genomics profiling method to genotype thousands of individual cells within tumors driven by transposon mutagenesis. This approach revealed a surprising genetic diversity among xenograft tumors and identified recurrent co-occurring mutations that emerge within distinct tumor subclones. Taken together, these observations reveal an unappreciated genetic complexity that drives BRAF inhibitor resistance.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"6 1","pages":"zcad061"},"PeriodicalIF":3.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139428199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN. 利用交互式神经母细胞瘤细胞系探索器 CLEAN 对 DNA 损伤反应途径进行临床前探索。

IF 3.4

NAR cancer Pub Date : 2024-01-11 eCollection Date: 2024-03-01 DOI: 10.1093/narcan/zcad062

Jonatan L Gabre, Peter Merseburger, Arne Claeys, Joachim Siaw, Sarah-Lee Bekaert, Frank Speleman, Bengt Hallberg, Ruth H Palmer, Jimmy Van den Eynden

{"title":"Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN.","authors":"Jonatan L Gabre, Peter Merseburger, Arne Claeys, Joachim Siaw, Sarah-Lee Bekaert, Frank Speleman, Bengt Hallberg, Ruth H Palmer, Jimmy Van den Eynden","doi":"10.1093/narcan/zcad062","DOIUrl":"10.1093/narcan/zcad062","url":null,"abstract":"Neuroblastoma (NB) is the most common cancer in infancy with an urgent need for more efficient targeted therapies. The development of novel (combinatorial) treatment strategies relies on extensive explorations of signaling perturbations in neuroblastoma cell lines, using RNA-Seq or other high throughput technologies (e.g. phosphoproteomics). This typically requires dedicated bioinformatics support, which is not always available. Additionally, while data from published studies are highly valuable and raw data (e.g. fastq files) are nowadays released in public repositories, data processing is time-consuming and again difficult without bioinformatics support. To facilitate NB research, more user-friendly and immediately accessible platforms are needed to explore newly generated as well as existing high throughput data. To make this possible, we developed an interactive data centralization and visualization web application, called CLEAN (the Cell Line Explorer web Application of Neuroblastoma data; https://ccgg.ugent.be/shiny/clean/). By focusing on the regulation of the DNA damage response, a therapeutic target of major interest in neuroblastoma, we demonstrate how CLEAN can be used to gain novel mechanistic insights and identify putative drug targets in neuroblastoma.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"6 1","pages":"zcad062"},"PeriodicalIF":3.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139428198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TSCRE: a comprehensive database for tumor-specific cis-regulatory elements. TSCRE：肿瘤特异性顺式调节元件综合数据库。

IF 3.4

NAR cancer Pub Date : 2024-01-11 eCollection Date: 2024-03-01 DOI: 10.1093/narcan/zcad063

Guanjie Peng, Bingyuan Liu, Mohan Zheng, Luowanyue Zhang, Huiqin Li, Mengni Liu, Yuan Liang, Tianjian Chen, Xiaotong Luo, Xianping Shi, Jian Ren, Yueyuan Zheng

{"title":"TSCRE: a comprehensive database for tumor-specific cis-regulatory elements.","authors":"Guanjie Peng, Bingyuan Liu, Mohan Zheng, Luowanyue Zhang, Huiqin Li, Mengni Liu, Yuan Liang, Tianjian Chen, Xiaotong Luo, Xianping Shi, Jian Ren, Yueyuan Zheng","doi":"10.1093/narcan/zcad063","DOIUrl":"10.1093/narcan/zcad063","url":null,"abstract":"Cis-regulatory elements (CREs) and super cis-regulatory elements (SCREs) are non-coding DNA regions which influence the transcription of nearby genes and play critical roles in development. Dysregulated CRE and SCRE activities have been reported to alter the expression of oncogenes and tumor suppressors, thereby regulating cancer hallmarks. To address the strong need for a comprehensive catalogue of dysregulated CREs and SCREs in human cancers, we present TSCRE (http://tscre.zsqylab.com/), an open resource providing tumor-specific and cell type-specific CREs and SCREs derived from the re-analysis of publicly available histone modification profiles. Currently, TSCRE contains 1 864 941 dysregulated CREs and 68 253 dysregulated SCREs identified from 1366 human patient samples spanning 17 different cancer types and 9 histone marks. Over 95% of these elements have been validated in public resources. TSCRE offers comprehensive annotations for each element, including associated genes, expression patterns, clinical prognosis, somatic mutations, transcript factor binding sites, cancer-type specificity, and drug response. Additionally, TSCRE integrates pathway and transcript factor enrichment analyses for each study, enabling in-depth functional and mechanistic investigations. Furthermore, TSCRE provides an interactive interface for users to explore any CRE and SCRE of interest. We believe TSCRE will be a highly valuable platform for the community to discover candidate cancer biomarkers.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"6 1","pages":"zcad063"},"PeriodicalIF":3.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139428200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Codelivery of TGFβ and Cox2 siRNA inhibits HCC by promoting T-cell penetration into the tumor and improves response to Immune Checkpoint Inhibitors. TGFβ和Cox2 siRNA联合递送可通过促进T细胞穿透肿瘤抑制HCC，并改善对免疫检查点抑制剂的反应。

IF 3.4

NAR cancer Pub Date : 2024-01-09 eCollection Date: 2024-03-01 DOI: 10.1093/narcan/zcad059

Wookhyun Kim, Zhou Ye, Vera Simonenko, Aashirwad Shahi, Asra Malikzay, Steven Z Long, John J Xu, Alan Lu, Jau-Hau Horng, Chang-Ru Wu, Pei-Jer Chen, Patrick Y Lu, David M Evans

{"title":"Codelivery of TGFβ and Cox2 siRNA inhibits HCC by promoting T-cell penetration into the tumor and improves response to Immune Checkpoint Inhibitors.","authors":"Wookhyun Kim, Zhou Ye, Vera Simonenko, Aashirwad Shahi, Asra Malikzay, Steven Z Long, John J Xu, Alan Lu, Jau-Hau Horng, Chang-Ru Wu, Pei-Jer Chen, Patrick Y Lu, David M Evans","doi":"10.1093/narcan/zcad059","DOIUrl":"10.1093/narcan/zcad059","url":null,"abstract":"Upregulation of TGFβ and Cox2 in the tumor microenvironment results in blockade of T-cell penetration into the tumor. Without access to tumor antigens, the T-cell response will not benefit from administration of the immune checkpoint antibodies. We created an intravenous polypeptide nanoparticle that can deliver two siRNAs (silencing TGFβ and Cox2). Systemic administration in mice, bearing a syngeneic orthotopic hepatocellular carcinoma (HCC), delivers the siRNAs to various cells in the liver, and significantly reduces the tumor. At 2 mg/kg (BIW) the nanoparticle demonstrated a single agent action and induced tumor growth inhibition to undetectable levels after five doses. Reducing the siRNAs to 1mg/kg BIW demonstrated greater inhibition in the presence of PD-L1 mAbs. After only three doses BIW, we could still recover a smaller tumor and, in tumor sections, showed an increase in penetration of CD4+ and CD8+ T-cells deeper into the remaining tumor that was not evident in animals treated with non-silencing siRNA. The combination of TGFβ and Cox2 siRNA co-administered in a polypeptide nanoparticle can act as a novel therapeutic alone against HCC and may augment the activity of the immune checkpoint antibodies. Silencing TGFβ and Cox2 converts an immune excluded (cold) tumor into a T-cell inflamed (hot) tumor.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"6 1","pages":"zcad059"},"PeriodicalIF":3.4,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CanVaxKB: a web-based cancer vaccine knowledgebase. CanVaxKB：基于网络的癌症疫苗知识库。

IF 3.2

NAR cancer Pub Date : 2024-01-09 eCollection Date: 2024-03-01 DOI: 10.1093/narcan/zcad060

Eliyas Asfaw, Asiyah Yu Lin, Anthony Huffman, Siqi Li, Madison George, Chloe Darancou, Madison Kalter, Nader Wehbi, Davis Bartels, Elyse Fleck, Nancy Tran, Daniel Faghihnia, Kimberly Berke, Ronak Sutariya, Farah Reyal, Youssef Tammam, Bin Zhao, Edison Ong, Zuoshuang Xiang, Virginia He, Justin Song, Andrey I Seleznev, Jinjing Guo, Yuanyi Pan, Jie Zheng, Yongqun He

{"title":"CanVaxKB: a web-based cancer vaccine knowledgebase.","authors":"Eliyas Asfaw, Asiyah Yu Lin, Anthony Huffman, Siqi Li, Madison George, Chloe Darancou, Madison Kalter, Nader Wehbi, Davis Bartels, Elyse Fleck, Nancy Tran, Daniel Faghihnia, Kimberly Berke, Ronak Sutariya, Farah Reyal, Youssef Tammam, Bin Zhao, Edison Ong, Zuoshuang Xiang, Virginia He, Justin Song, Andrey I Seleznev, Jinjing Guo, Yuanyi Pan, Jie Zheng, Yongqun He","doi":"10.1093/narcan/zcad060","DOIUrl":"10.1093/narcan/zcad060","url":null,"abstract":"Cancer vaccines have been increasingly studied and developed to prevent or treat various types of cancers. To systematically survey and analyze different reported cancer vaccines, we developed CanVaxKB (https://violinet.org/canvaxkb), the first web-based cancer vaccine knowledgebase that compiles over 670 therapeutic or preventive cancer vaccines that have been experimentally verified to be effective at various stages. Vaccine construction and host response data are also included. These cancer vaccines are developed against various cancer types such as melanoma, hematological cancer, and prostate cancer. CanVaxKB has stored 263 genes or proteins that serve as cancer vaccine antigen genes, which we have collectively termed 'canvaxgens'. Top three mostly used canvaxgens are PMEL, MLANA and CTAG1B, often targeting multiple cancer types. A total of 193 canvaxgens are also reported in cancer-related ONGene, Network of Cancer Genes and/or Sanger Cancer Gene Consensus databases. Enriched functional annotations and clusters of canvaxgens were identified and analyzed. User-friendly web interfaces are searchable for querying and comparing cancer vaccines. CanVaxKB cancer vaccines are also semantically represented by the community-based Vaccine Ontology to support data exchange. Overall, CanVaxKB is a timely and vital cancer vaccine source that facilitates efficient collection and analysis, further helping researchers and physicians to better understand cancer mechanisms.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"6 1","pages":"zcad060"},"PeriodicalIF":3.2,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An impaired ubiquitin-proteasome system increases APOBEC3A abundance. 泛素-蛋白酶体系统受损会增加 APOBEC3A 的丰度。

IF 3.4

NAR cancer Pub Date : 2023-12-19 eCollection Date: 2023-12-01 DOI: 10.1093/narcan/zcad058

Margo Coxon, Madeline A Dennis, Alexandra Dananberg, Christopher D Collins, Hannah E Wilson, Jordyn Meekma, Marina I Savenkova, Daniel Ng, Chelsea A Osbron, Tony M Mertz, Alan G Goodman, Sascha H Duttke, John Maciejowski, Steven A Roberts

{"title":"An impaired ubiquitin-proteasome system increases APOBEC3A abundance.","authors":"Margo Coxon, Madeline A Dennis, Alexandra Dananberg, Christopher D Collins, Hannah E Wilson, Jordyn Meekma, Marina I Savenkova, Daniel Ng, Chelsea A Osbron, Tony M Mertz, Alan G Goodman, Sascha H Duttke, John Maciejowski, Steven A Roberts","doi":"10.1093/narcan/zcad058","DOIUrl":"10.1093/narcan/zcad058","url":null,"abstract":"Apolipoprotein B messenger RNA (mRNA) editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases cause genetic instability during cancer development. Elevated APOBEC3A (A3A) levels result in APOBEC signature mutations; however, mechanisms regulating A3A abundance in breast cancer are unknown. Here, we show that dysregulating the ubiquitin-proteasome system with proteasome inhibitors, including Food and Drug Administration-approved anticancer drugs, increased A3A abundance in breast cancer and multiple myeloma cell lines. Unexpectedly, elevated A3A occurs via an ∼100-fold increase in A3A mRNA levels, indicating that proteasome inhibition triggers a transcriptional response as opposed to or in addition to blocking A3A degradation. This transcriptional regulation is mediated in part through FBXO22, a protein that functions in SKP1-cullin-F-box ubiquitin ligase complexes and becomes dysregulated during carcinogenesis. Proteasome inhibitors increased cellular cytidine deaminase activity, decreased cellular proliferation and increased genomic DNA damage in an A3A-dependent manner. Our findings suggest that proteasome dysfunction, either acquired during cancer development or induced therapeutically, could increase A3A-induced genetic heterogeneity and thereby influence therapeutic responses in patients.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"5 4","pages":"zcad058"},"PeriodicalIF":3.4,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10753533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Detection of oxaliplatin- and cisplatin-DNA lesions requires different global genome repair mechanisms that affect their clinical efficacy. 检测奥沙利铂和顺铂dna病变需要不同的全基因组修复机制，从而影响其临床疗效。

IF 3.4

NAR cancer Pub Date : 2023-12-05 eCollection Date: 2023-12-01 DOI: 10.1093/narcan/zcad057

Jana Slyskova, Alba Muniesa-Vargas, Israel Tojal da Silva, Rodrigo Drummond, Jiyeong Park, David Häckes, Isabella Poetsch, Cristina Ribeiro-Silva, Amandine Moretton, Petra Heffeter, Orlando D Schärer, Wim Vermeulen, Hannes Lans, Joanna I Loizou

{"title":"Detection of oxaliplatin- and cisplatin-DNA lesions requires different global genome repair mechanisms that affect their clinical efficacy.","authors":"Jana Slyskova, Alba Muniesa-Vargas, Israel Tojal da Silva, Rodrigo Drummond, Jiyeong Park, David Häckes, Isabella Poetsch, Cristina Ribeiro-Silva, Amandine Moretton, Petra Heffeter, Orlando D Schärer, Wim Vermeulen, Hannes Lans, Joanna I Loizou","doi":"10.1093/narcan/zcad057","DOIUrl":"10.1093/narcan/zcad057","url":null,"abstract":"The therapeutic efficacy of cisplatin and oxaliplatin depends on the balance between the DNA damage induction and the DNA damage response of tumor cells. Based on clinical evidence, oxaliplatin is administered to cisplatin-unresponsive cancers, but the underlying molecular causes for this tumor specificity are not clear. Hence, stratification of patients based on DNA repair profiling is not sufficiently utilized for treatment selection. Using a combination of genetic, transcriptomics and imaging approaches, we identified factors that promote global genome nucleotide excision repair (GG-NER) of DNA-platinum adducts induced by oxaliplatin, but not by cisplatin. We show that oxaliplatin-DNA lesions are a poor substrate for GG-NER initiating factor XPC and that DDB2 and HMGA2 are required for efficient binding of XPC to oxaliplatin lesions and subsequent GG-NER initiation. Loss of DDB2 and HMGA2 therefore leads to hypersensitivity to oxaliplatin but not to cisplatin. As a result, low DDB2 levels in different colon cancer cells are associated with GG-NER deficiency and oxaliplatin hypersensitivity. Finally, we show that colon cancer patients with low DDB2 levels have a better prognosis after oxaliplatin treatment than patients with high DDB2 expression. We therefore propose that DDB2 is a promising predictive marker of oxaliplatin treatment efficiency in colon cancer.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"5 4","pages":"zcad057"},"PeriodicalIF":3.4,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0