NAR cancer最新文献_第5页

Exploiting nanopore sequencing advances for tRNA sequencing of human cancer models. 利用纳米孔测序技术对人类癌症模型进行tRNA测序。

IF 4.6

NAR cancer Pub Date : 2025-11-03 eCollection Date: 2025-12-01 DOI: 10.1093/narcan/zcaf044

Adva Kochavi, Arno Velds, Maya Suzuki, Shinichiro Akichika, Tsutomu Suzuki, Roderick L Beijersbergen, Reuven Agami

{"title":"Exploiting nanopore sequencing advances for tRNA sequencing of human cancer models.","authors":"Adva Kochavi, Arno Velds, Maya Suzuki, Shinichiro Akichika, Tsutomu Suzuki, Roderick L Beijersbergen, Reuven Agami","doi":"10.1093/narcan/zcaf044","DOIUrl":"10.1093/narcan/zcaf044","url":null,"abstract":"Transfer RNAs (tRNAs) are essential regulators of protein synthesis, and dysregulation of their abundance and modification status is involved in many human diseases including cancer. Despite the rapid development of novel tRNA sequencing approaches, due to tRNAs' stable secondary structure and abundant modification sites, the human tRNA landscape has remained mostly unexplored. Here, we evaluated the new RNA004 chemistry of Oxford Nanopore Technologies, that is integrated with updated Dorado base-caller models, for tRNA quantification and modification annotation in human cancer models. We demonstrated that this technology identifies variations in tRNA expression across cancer cell lines and in response to external stress conditions, with highly reproducible results. We also show that analysis of base-calling error rate can indicate the presence of known modifications, including the cancer-associated tRNAPhe-Wybutosine modification. Furthermore, implementing the updated Dorado modification-calling feature, we showed the potential of RNA004 tRNA-seq in predicting common tRNA modifications. We also pinpointed possible limitations and challenges associated with both modification calling methods. Overall, RNA004 tRNA-seq can potentially enhance our understanding of the human tRNAome by simultaneously analyzing both tRNA abundance and modifications.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 4","pages":"zcaf044"},"PeriodicalIF":4.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12582020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446946","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

Brain tumor classification from FFPE samples using nanopore methylation sequencing. 利用纳米孔甲基化测序对FFPE样本进行脑肿瘤分类。

IF 4.6

NAR cancer Pub Date : 2025-10-30 eCollection Date: 2025-12-01 DOI: 10.1093/narcan/zcaf038

Galina Feinberg-Gorenshtein, Assaf Grunwald, Carlo Vermeulen, Nurit Gal Mark, Elena Shinderman-Maman, Adva Levy-Barda, Keren Shichrur, Michal Hameiri-Grossman, Orli Michaeli, Shira Amar, Suzanna Fichman, Abraham Natan, Tali Siegal, Shlomit Yust-Katz, Hanna Weiss, Osnat Konen, Amir Kershenovich, Andrew A Kanner, Jeroen de Ridder, Helen Toledano, Shai Izraeli, Yehudit Birger, Yuval Ebenstein

{"title":"Brain tumor classification from FFPE samples using nanopore methylation sequencing.","authors":"Galina Feinberg-Gorenshtein, Assaf Grunwald, Carlo Vermeulen, Nurit Gal Mark, Elena Shinderman-Maman, Adva Levy-Barda, Keren Shichrur, Michal Hameiri-Grossman, Orli Michaeli, Shira Amar, Suzanna Fichman, Abraham Natan, Tali Siegal, Shlomit Yust-Katz, Hanna Weiss, Osnat Konen, Amir Kershenovich, Andrew A Kanner, Jeroen de Ridder, Helen Toledano, Shai Izraeli, Yehudit Birger, Yuval Ebenstein","doi":"10.1093/narcan/zcaf038","DOIUrl":"10.1093/narcan/zcaf038","url":null,"abstract":"Oxford Nanopore Technology (ONT)-based methylation sequencing is emerging as a powerful approach for the rapid and accurate classification of brain tumors, an essential component of precision oncology. However, its broader clinical adoption has been limited by reliance on fresh-frozen (FF) tissue, whereas the vast majority of clinical specimens are formalin-fixed paraffin-embedded (FFPE). In this study, we address this limitation by evaluating the effects of FFPE processing on DNA methylation profiles and introducing a validated protocol for ONT-based classification using DNA extracted directly from pathology-marked regions on stained FFPE slides. This approach enables the targeted selection of tumor-rich areas following histological assessment, thereby improving DNA input quality and tumor content. We demonstrate that even small, low-input samples (≥25 ng) can be successfully classified using this method, with high concordance to final integrated neuropathological diagnoses. Our results show that, despite modest methylation loss associated with formalin fixation, classification performance remains robust. Notably, we identify a correlation between methylation degradation and fixation time, supporting a recommendation to limit formalin exposure to ≤3-4 days when possible. By enabling accurate methylation-based tumor classification from routinely processed, stained FFPE tissue, our protocol integrates seamlessly into existing clinical workflows. This expands the accessibility of ONT-based diagnostics and supports informed, timely treatment decisions-even in cases with minimal tissue availability or urgent clinical need.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 4","pages":"zcaf038"},"PeriodicalIF":4.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433575","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

G-quadruplex ligand RHPS4 compromises cellular radioresistance by inhibiting the mitochondrial adaptive response induced by ionizing irradiation. g -四重配体RHPS4通过抑制电离辐射诱导的线粒体适应性反应来降低细胞的辐射抗性。

IF 4.6

NAR cancer Pub Date : 2025-10-30 eCollection Date: 2025-12-01 DOI: 10.1093/narcan/zcaf033

Sabine Tricot, Capucine Siberchicot, Isaline Bontemps, Chantal Desmaze, Gueorgui Kratassiouk, Marie Vandamme, Guillaume Pinna, Ivan Nemazanyy, J Pablo Radicella, Guy Lenaers, Xavier Renaudin, Jérome Lebeau, Anna Campalans

{"title":"G-quadruplex ligand RHPS4 compromises cellular radioresistance by inhibiting the mitochondrial adaptive response induced by ionizing irradiation.","authors":"Sabine Tricot, Capucine Siberchicot, Isaline Bontemps, Chantal Desmaze, Gueorgui Kratassiouk, Marie Vandamme, Guillaume Pinna, Ivan Nemazanyy, J Pablo Radicella, Guy Lenaers, Xavier Renaudin, Jérome Lebeau, Anna Campalans","doi":"10.1093/narcan/zcaf033","DOIUrl":"10.1093/narcan/zcaf033","url":null,"abstract":"A major challenge in radiotherapy is to enhance tumour cell sensitivity to radiation while minimizing damage to healthy tissues. Enhancing the effectiveness of radiotherapy can be achieved by combining irradiation with small radiosensitizing molecules, which promote cancer cell death and allow for reduced radiation doses, thereby limiting harm to surrounding healthy tissues. Since mitochondria play a key role in tumour cell proliferation, they represent a promising therapeutic target for cancer treatment. In this study, we characterized the impact of irradiation on mitochondrial function in radioresistant cancer cells. Our findings revealed several adaptive responses that may contribute to radioresistance, including increased mitochondrial DNA (mtDNA) content, mitochondrial mass, enhanced activity, and hyperfusion of the mitochondrial network. Notably, the use of mitochondrial-targeted G-quadruplex (G4) ligands, which block mtDNA replication and transcription, disrupted these responses, reducing cancer cell survival in a mtDNA-dependent manner. These results demonstrate that mitochondrial adaptations contribute to radioresistance and highlight mitochondria as a novel target for the radiosensitizing effects of G4 ligands.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 4","pages":"zcaf033"},"PeriodicalIF":4.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433579","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

THRESHOLD: a comprehensive transcriptomic analysis tool for evaluating gene saturation and impact in disease progression. THRESHOLD：一个全面的转录组学分析工具，用于评估基因饱和度和疾病进展的影响。

IF 4.6

NAR cancer Pub Date : 2025-10-30 eCollection Date: 2025-12-01 DOI: 10.1093/narcan/zcaf032

Finán Gammell, Jennifer Li, Christopher Elco, Jessica Plavicki, Alper Uzun

{"title":"THRESHOLD: a comprehensive transcriptomic analysis tool for evaluating gene saturation and impact in disease progression.","authors":"Finán Gammell, Jennifer Li, Christopher Elco, Jessica Plavicki, Alper Uzun","doi":"10.1093/narcan/zcaf032","DOIUrl":"10.1093/narcan/zcaf032","url":null,"abstract":"Gene expression studies are fundamental in molecular biology, offering insights into development, disease progression, and therapeutic targets. To address the need for precise analysis of large datasets, we developed THRESHOLD, a novel tool that introduces the concept of gene saturation. Unlike traditional methods focused on absolute or binary expression levels, THRESHOLD quantifies the consistency of gene expression across patients, revealing co-regulation patterns critical for understanding disease mechanisms and stratifying patients by molecular signatures. The tool offers several features, including user-defined parameters, statistical comparisons, and interactive data visualization. THRESHOLD has uncovered compelling insights into disease progression using TCGA cancer datasets. For instance, bladder urothelial carcinoma demonstrated increasing upregulated gene saturation in progressive cancer stages (P < .00001). Moreover, THRESHOLD identified heightened gene saturation in patients with earlier onset of prostate adenocarcinoma (P < .0001) and revealed a critical fusion transcript, SLC45A2-AMACR, implicated in prostate adenocarcinoma progression, recurrence, and metastasis. Additionally, novel biomarkers and potential candidates for drug therapies were identified through protein-protein interaction networks and functional analyses of saturation data in colon adenocarcinoma and breast invasive carcinoma. THRESHOLD offers a new approach for studying gene expression dynamics and patient stratification. The tool is publicly available at Zenodo: https://zenodo.org/records/15287195.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 4","pages":"zcaf032"},"PeriodicalIF":4.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433620","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

Reference-free RNA profiling predicts triple negative breast cancer chemoresistance to neoadjuvant treatment. 无参考RNA谱预测三阴性乳腺癌对新辅助治疗的化疗耐药。

IF 4.6

NAR cancer Pub Date : 2025-10-07 eCollection Date: 2025-12-01 DOI: 10.1093/narcan/zcaf036

Nouritza Torossian, Marc Gabriel, Panagiotis Papoutsoglou, Dominika Foretek, Camille Brochard, Maud Kamal, Linda Ramdani, Constance Lamy, Charlotte Lecerf, Maral Halladjian, Celia Dupain, Josiane Lafleur, Adriana Aguilar-Mahecha, Mark Basik, Anne Vincent-Salomon, Christophe L E Tourneau, Sergio Roman-Roman, Daniel Gautheret, Antonin Morillon

{"title":"Reference-free RNA profiling predicts triple negative breast cancer chemoresistance to neoadjuvant treatment.","authors":"Nouritza Torossian, Marc Gabriel, Panagiotis Papoutsoglou, Dominika Foretek, Camille Brochard, Maud Kamal, Linda Ramdani, Constance Lamy, Charlotte Lecerf, Maral Halladjian, Celia Dupain, Josiane Lafleur, Adriana Aguilar-Mahecha, Mark Basik, Anne Vincent-Salomon, Christophe L E Tourneau, Sergio Roman-Roman, Daniel Gautheret, Antonin Morillon","doi":"10.1093/narcan/zcaf036","DOIUrl":"10.1093/narcan/zcaf036","url":null,"abstract":"Triple negative breast cancer (TNBC) is the most aggressive breast cancer (BC) and often affects young women. TNBCs are highly heterogeneous and do not benefit from personalized medicine at localized stages. Most TNBC patients undergo neoadjuvant chemotherapy (NAC) before surgery. In case of chemoresistance with residual tumor after NAC, survival is poor despite execution of complete tumor resection. There is currently no clinically useful biomarker to predict TNBC chemoresistance to NAC that would enable targeted therapeutic intensification. We analyzed here a unique cohort of 106 TNBC tumors before NAC, including 58 chemoresistant and 48 chemosensitive cases, from 2 independent hospitals. Using machine learning under a nested cross-validation design, we obtained two transcriptomic signatures respectively generated from standard differential gene expression analysis and reference-free analysis of differential fragments of transcripts, without any annotation bias. This approach resulted in accurate signatures of TNBC chemoresistance to NAC. Gene ontology analyses of reference-free signatures highlighted DNA repair, replication, and metabolism, in agreement with current knowledge of TNBC resistance biology. In summary, these results show the potential of a reference-free generated transcriptomic signature as predictive biomarker of early TNBC chemoresistance.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 4","pages":"zcaf036"},"PeriodicalIF":4.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254388","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

Co-expression of CD30 and SLFN11 serves as a dual biomarker for the treatment of cutaneous T-cell lymphoma. CD30和SLFN11的共表达可作为治疗皮肤t细胞淋巴瘤的双重生物标志物。

IF 4.6

NAR cancer Pub Date : 2025-10-07 eCollection Date: 2025-12-01 DOI: 10.1093/narcan/zcaf037

Takatoshi Shimauchi, Junko Murai, Manami Iwasaki, Pawit Phadungsaksawasdi, Toshiyuki Ojima, Kazuyasu Fujii, Tetsuya Honda

{"title":"Co-expression of CD30 and SLFN11 serves as a dual biomarker for the treatment of cutaneous T-cell lymphoma.","authors":"Takatoshi Shimauchi, Junko Murai, Manami Iwasaki, Pawit Phadungsaksawasdi, Toshiyuki Ojima, Kazuyasu Fujii, Tetsuya Honda","doi":"10.1093/narcan/zcaf037","DOIUrl":"10.1093/narcan/zcaf037","url":null,"abstract":"Advanced-stage cutaneous T-cell lymphoma (CTCL) is treated with diverse modalities, including DNA-damaging agents, anti-CD30 antibody-drug conjugates, and histone deacetylase (HDAC) inhibitors. Schlafen 11 (SLFN11) has emerged as a key determinant of sensitivity to DNA-damaging agents, yet its role in CTCL remains unclear. Here, we examined SLFN11 expression in two major CTCL subtypes-mycosis fungoides (MF) and Sézary syndrome (SS). Immunohistochemistry revealed SLFN11 positivity in 52% of MF (13/25) and 80% of SS (4/5) cases, with multivariate analysis showing a significant correlation between SLFN11 and CD30 expression. In normal human peripheral blood mononuclear cells, CD3/CD28/IL-2 stimulation induced co-expression of SLFN11 and CD30 in T cells, which was accompanied by heightened sensitivity to DNA-damaging agents. The JAK inhibitor cerdulatinib suppressed both markers. Among five CTCL cell lines, HUT78-expressing the highest SLFN11 levels-was the most sensitive to DNA-damaging agents, whereas SLFN11 knockout conferred resistance. Attempts to restore SLFN11 expression in SLFN11-low CTCL cells using six (pre)clinical HDAC inhibitors produced inconsistent results across cell lines and drugs. Together, these findings identify SLFN11 and CD30 as co-expressed therapeutic targets in CTCL and support the rationale for CD30-directed antibody-DNA-damaging agent conjugates as a precision treatment strategy.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 4","pages":"zcaf037"},"PeriodicalIF":4.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254334","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

Androgen receptor inhibition extends PARP inhibitor activity in prostate cancer models beyond BRCA mutations and defects in homologous recombination repair. 雄激素受体抑制将PARP抑制剂在前列腺癌模型中的活性扩展到BRCA突变和同源重组修复缺陷之外。

IF 4.6

NAR cancer Pub Date : 2025-10-07 eCollection Date: 2025-12-01 DOI: 10.1093/narcan/zcaf035

Giuditta Illuzzi, Alessandro Galbiati, Anna D Staniszewska, Robert Hanson, Chrysiis Michaloglou, Sophie L Cooke, Karolina Uznańska, Maja Białecka, Kamil Solarczyk, Harveer S Dev, Charlie E Massie, Mark R Albertella, Elisabetta Leo, Josep V Forment, Mark J O'Connor

{"title":"Androgen receptor inhibition extends PARP inhibitor activity in prostate cancer models beyond BRCA mutations and defects in homologous recombination repair.","authors":"Giuditta Illuzzi, Alessandro Galbiati, Anna D Staniszewska, Robert Hanson, Chrysiis Michaloglou, Sophie L Cooke, Karolina Uznańska, Maja Białecka, Kamil Solarczyk, Harveer S Dev, Charlie E Massie, Mark R Albertella, Elisabetta Leo, Josep V Forment, Mark J O'Connor","doi":"10.1093/narcan/zcaf035","DOIUrl":"10.1093/narcan/zcaf035","url":null,"abstract":"Clinical trials show benefit of the combination of poly(ADP-ribose) polymerase inhibitors (PARPi) with androgen receptor (AR) pathway inhibitors (ARPi) in metastatic, castration-resistant prostate cancer. While benefit was evident in patients with tumours harbouring mutations in homologous recombination repair (HRR) genes, improved outcomes were also observed in the absence of such alterations. Although there is literature linking AR with DNA repair, the basis of the interaction between the AR and PARP is unclear. We show that benefit of the combination of ARPi and PARPi in prostate cancer models with no HRR mutations requires ARPi-responsive cells and a PARPi with PARP1-trapping activity, and does not involve an effect of PARPi treatment in modulating AR transcription. Combination benefit is driven by an increase in DNA double-strand breaks and micronuclei formation, which is not due to a control of HRR gene transcription by the AR. Also, we uncover a novel role of PARP1 modulating AR recruitment to chromatin in the presence of DNA damage. These data shed light on the interplay between PARP1 and the AR in dealing with genotoxic insults and provide a mechanism-of-action consistent with the clinical benefit of the combination of PARPi and ARPi in patients with prostate cancer.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 4","pages":"zcaf035"},"PeriodicalIF":4.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254290","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

DNA repair helicases: from mechanistic understanding to therapeutic implications. DNA修复解旋酶：从机理认识到治疗意义。

IF 4.6

NAR cancer Pub Date : 2025-10-07 eCollection Date: 2025-12-01 DOI: 10.1093/narcan/zcaf034

Vijay Menon, Susan E Gueble

{"title":"DNA repair helicases: from mechanistic understanding to therapeutic implications.","authors":"Vijay Menon, Susan E Gueble","doi":"10.1093/narcan/zcaf034","DOIUrl":"10.1093/narcan/zcaf034","url":null,"abstract":"The maintenance of genomic integrity is paramount for normal cell physiology and survival as well as avoidance of carcinogenesis. Cellular DNA is periodically subjected to a myriad of exogenous and endogenous threats and requires constant monitoring to limit genomic instability. To this end, cells possess an intricate DNA damage response and repair (DDR) module comprised of different classes of protein players. The DNA helicases, ATP-dependent enzymes that unwind the DNA double helix, are one such important class of proteins, which act as a linchpin between the recognition and resolution of DNA damage via facilitating various DNA repair processes. Dysfunction or absence of DDR helicase function is implicated in several human disorders including Bloom syndrome, Werner syndrome, Rothmund-Thomson syndrome, and Fanconi anemia. Somatic helicase mutations or dysregulation of helicase function can also contribute to cancer development, progression, and chemotherapy sensitivity, making helicases a promising target class for chemotherapeutic drug intervention. In addition, recent discoveries have identified some DDR helicases in novel synthetic lethal interactions. In this critical review, we will focus on human DNA helicases that are directly or indirectly involved in DDR with special emphasis on their mechanistic actions and clinical implications.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 4","pages":"zcaf034"},"PeriodicalIF":4.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254316","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

Analysis of the mRNA modification machinery alterations in breast cancer through the SCAN-B cohort. 通过SCAN-B队列分析乳腺癌mRNA修饰机制的改变。

IF 4.6

NAR cancer Pub Date : 2025-09-03 eCollection Date: 2025-09-01 DOI: 10.1093/narcan/zcaf027

Carlos Peula, Margalida Esteva-Socias, Kanchan Kumari, Erik Dassi, Francesca Aguilo

引用次数: 0

Neural interaction explainable AI predicts drug response across cancers. 神经相互作用可解释的AI预测癌症的药物反应。

IF 4.6

NAR cancer Pub Date : 2025-09-03 eCollection Date: 2025-09-01 DOI: 10.1093/narcan/zcaf029

Philipp Keyl, Julius Keyl, Andreas Mock, Gabriel Dernbach, Liliana H Mochmann, Niklas Kiermeyer, Philipp Jurmeister, Michael Bockmayr, Roland F Schwarz, Grégoire Montavon, Klaus-Robert Müller, Frederick Klauschen

{"title":"Neural interaction explainable AI predicts drug response across cancers.","authors":"Philipp Keyl, Julius Keyl, Andreas Mock, Gabriel Dernbach, Liliana H Mochmann, Niklas Kiermeyer, Philipp Jurmeister, Michael Bockmayr, Roland F Schwarz, Grégoire Montavon, Klaus-Robert Müller, Frederick Klauschen","doi":"10.1093/narcan/zcaf029","DOIUrl":"10.1093/narcan/zcaf029","url":null,"abstract":"Personalized treatment selection is crucial for cancer patients due to the high variability in drug response. While actionable mutations can increasingly inform treatment decisions, most therapies still rely on population-based approaches. Here, we introduce neural interaction explainable AI (NeurixAI), an explainable and highly scalable deep learning framework that models drug-gene interactions and identifies transcriptomic patterns linked with drug response. Trained on data from 546 646 drug perturbation experiments involving 1135 drugs and molecular profiles from 476 tumors, NeurixAI accurately predicted treatment responses for 272 targeted and 30 chemotherapeutic drugs in unseen tumor samples (Spearman's rho >0.2), maintaining high performance on an external validation set. Additionally, NeurixAI identified the anticancer potential of 160 repurposed non-cancer drugs. Using explainable artificial intelligence (xAI), our framework uncovered key genes influencing drug response at the individual tumor level and revealed both known and novel mechanisms of drug resistance. These findings demonstrate the potential of integrating transcriptomics with xAI to optimize cancer treatment, enable drug repurposing, and identify new therapeutic targets.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"7 3","pages":"zcaf029"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016961","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