OncoTargets and therapy最新文献

{"title":"Characterization of Patients with EGFR Mutation-Positive NSCLC Following Emergence of the Osimertinib Resistance Mutations, L718Q or G724S: A Multicenter Retrospective Observational Study in France","authors":"Mateo Sanchis-Borja, Florian Guisier, Aurélie Swalduz, Hubert Curcio, Victor Basse, Christophe Maritaz, Christos Chouaid, Jean-Bernard Auliac","doi":"10.2147/ott.s448909","DOIUrl":"https://doi.org/10.2147/ott.s448909","url":null,"abstract":"<strong>Purpose:</strong> The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is an effective first-line therapy for patients with common <em>EGFR</em> mutation-positive non-small cell lung cancer (NSCLC). However, almost all patients become resistant to treatment. In some patients, emergence of tertiary <em>EGFR</em> mutations is implicated as a resistance mechanism. This study describes patients with NSCLC who acquired the rare <em>EGFR</em> mutations, L718Q or G724S, following EGFR TKI treatment.<br/><strong>Patients and Methods:</strong> This was a retrospective, observational study undertaken in France from Feb–Nov 2021, in patients with <em>EGFR</em> mutation-positive NSCLC with an acquired L718Q or G724S mutation. Primary objectives were description of tumor characteristics, progression, and progression under treatment.<br/><strong>Results:</strong> Nine eligible patients were identified. Acquired resistance to initial EGFR TKI treatment was associated with T790M emergence in six patients, who then received osimertinib monotherapy. Overall, eight patients received osimertinib monotherapy treatment at some point (average treatment duration: 18.3 months). Following the emergence of L718Q or G724S, patients received chemotherapy (n = 4; two of whom subsequently received afatinib), nivolumab (n = 2), afatinib (n = 2), or immunochemotherapy (n = 1). In the four patients who received afatinib after identification of L718Q or G724S, 2 achieved a partial response, one had stable disease and one had progressive disease. Treatment duration was 1.6– 31.7 months. In patients with controlled disease (n = 3), progression-free survival was 6.1– 31.7 months. Two of these patients had previously received osimertinib.<br/><strong>Conclusion:</strong> Currently, there is no consensus regarding the treatment of <em>EGFR</em> mutation-positive NSCLC following emergence of the osimertinib resistance mutations, L718Q or G724S. Afatinib appears to be a promising treatment option in this setting.<br/><br/><strong>Keywords:</strong> osimertinib, afatinib, real-world evidence, tertiary <em>EGFR</em> mutations<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141165649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of Nicotinamide Metabolism-Related Gene Signatures as a Novel Prognostic Model for Hepatocellular Carcinoma","authors":"Sijia Yang, Ang Li, Lihong Lv, Jinxin Duan, Zhihua Zheng, Wenfeng Zhuo, Jun Min, Jinxing Wei","doi":"10.2147/ott.s464709","DOIUrl":"https://doi.org/10.2147/ott.s464709","url":null,"abstract":"<strong>Background:</strong> Nicotinamide (NAM+) regulates redox and metabolic activities in the mitochondria. The intention of the research was to identify key genes that relate to nicotinamide in hepatocellular carcinoma (HCC).<br/><strong>Methods:</strong> Relevant clinical information were collected as well as RNA-seq data using the Cancer Genome Atlas (TCGA) database. Differential analysis was used to discover the genes that were differently expressed. On the key genes associated with NAM, functional enrichment analysis was carried out. Next, receiver operating characteristic (ROC) and prognosis Kaplan-Meier (K-M) curve analyses were used to evaluate the importance of important gene expression, respectively. The immune cell signatures were estimated using the CIBERSORT algorithm. Finally, the anticancer impact of NAM on HCC was experimentally confirmed, and important genes NADSYN1 and NT5C were validated at the protein level in clinical specimens.<br/><strong>Results:</strong> Six prognostic key genes (NAXE, NADSYN1, NT5C, NT5C3A, PNP and NT5E) were identified. There is an association between the level of key gene expression and the clinical prognosis. Four key genes (NAXE, NADSYN1, NT5C and NT5C3A) have statistical significance of survival prognosis. Finally, the expression of NAM-related genes and the inhibitory effect of NAM on HCC were verified by experiments.<br/><strong>Conclusion:</strong> The study first found some Nicotinamide metabolism-related differentially expressed genes (NMRDEGs) that are related to HCC can contribute to predicting survival and monitoring the treatment.<br/><br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141165644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MCM5 is a Novel Therapeutic Target for Glioblastoma","authors":"Jian Zhou, Housheng Zheng, Huiru Zhang, Wenqiang Yu, Baoer Li, Liang Ye, Lu Wang","doi":"10.2147/ott.s457600","DOIUrl":"https://doi.org/10.2147/ott.s457600","url":null,"abstract":"<strong>Objective:</strong> MCM5 is a DNA licensing factor involved in cell proliferation and has been previously established as an excellent biomarker in a number of malignancies. Nevertheless, the role of MCM5 in GBM has not been fully clarified. The present study aimed to investigate the potential roles of MCM5 in the treatment of GBM and to elucidate its underlying mechanism, which is beneficial for developing new therapeutic strategies and predicting prognosis.<br/><strong>Methods:</strong> Firstly, we obtained transcriptomic and proteomic data from the TCGA and CPTAC databases on glioma patients. Employing the DeSeq2 R package, we then identified genes with joint differential expression in GBM tissues subjected to chemotherapy. To develop a prognostic risk score model, we performed univariate and multivariate Cox regression analyses. In vitro knockdown and overexpression of MCM5 were used to further investigate the biological functions of GBM cells. Additionally, we also delved into the upstream regulation of MCM5, revealing associations with several transcription factors. Finally, we investigated differences in immune cell infiltration and drug sensitivity across diverse risk groups identified in the prognostic risk model.<br/><strong>Results:</strong> In this study, the chemotherapy-treated GBM samples exhibited consistent alterations in 46 upregulated and 94 downregulated genes at both the mRNA and protein levels. Notably, MCM5 emerged as a gene with prognostic significance as well as potential therapeutic relevance. In vitro experiments subsequently validated the role of increased MCM5 expression in promoting GBM cell proliferation and resistance to TMZ. Correlations with transcription factors such as CREB1, CTCF, NFYB, NRF1, PBX1, TEAD1, and USF1 were discovered during upstream regulatory analysis, enriching our understanding of MCM5 regulatory mechanisms. The study additionally delves into immune cell infiltration and drug sensitivity, providing valuable insights for personalized treatment approaches.<br/><strong>Conclusion:</strong> This study identifies MCM5 as a key player in GBM, demonstrating its prognostic significance and potential therapeutic relevance by elucidating its role in promoting cell proliferation and resistance to chemotherapy.<br/><br/><strong>Keywords:</strong> glioblastoma, minichromosome maintenance protein 5, chemotherapeutic drug resistance<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140927974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Noncoding RNA NEAT1 Promotes Cell Proliferation and Invasion and Suppresses Apoptosis in Hepatocellular Carcinoma by Regulating miRNA-22-3p/akt2 in vitro and in vivo [Retraction]","authors":"Xichang Zhou, Xiang Wang, Yizhou Zhou, Long Cheng, Youwei Zhang, Yangmei Zhang","doi":"10.2147/ott.s476432","DOIUrl":"https://doi.org/10.2147/ott.s476432","url":null,"abstract":"Retraction for the article Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140887807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synchronous Multiple Primary Malignant Adenocarcinoma of the Descending Colon and Fungating Bleeding Adenocarcinoma of the Terminal Ileum Presenting Massive Rectal Bleeding: A Trap for the Unwary","authors":"Baicheng Li, Zhao Chen, Guangzhi Wang, Yaqing Liu, Shili Ning","doi":"10.2147/ott.s453682","DOIUrl":"https://doi.org/10.2147/ott.s453682","url":null,"abstract":"<strong>Abstract:</strong> Primary cancer of the ileum is rare, and when it occurs in conjunction with primary colon cancer, it becomes even more infrequent and challenging to diagnose prior to surgical intervention. Primary small bowel cancers can be overlooked and may be misidentified as small bowel mesenchymal tumours or advanced metastases from colon cancer. We present an exceedingly uncommon case of ruptured primary ileal cancer combined with primary descending colon cancer presenting with gastrointestinal bleeding. Based on our understanding, instances of dual tumours concurrently occurring are exceedingly infrequent. In this patient, there was a preoperative suspicion of bleeding from colon cancer in the descending region. However, intraoperative exploration revealed that the location of the bleeding was a terminal ileal mass. Following the surgical intervention, the patient recovered satisfactorily. Intraoperative exploration of the entire gastrointestinal tract is therefore necessary in patients with gastrointestinal haemorrhage, especially in those who require urgent surgery without adequate preoperative investigations. If a mass is detected at the end of the ileum, intraoperative pathology should be performed if feasible. Subsequently, if the diagnosis reveals an adenocarcinoma, terminal ileocolic resection and right hemicolectomy are necessary for appropriate resection.<br/><br/><strong>Keywords:</strong> multiple primary malignant neoplasms, gut bleeding, adenocarcinoma of the small bowel, descending colon cancer, gastrointestinal tumours, case report<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNA-99b-5p Targets FZD8 to Inhibit Non-Small Cell Lung Cancer Proliferation, Migration and Invasion [Retraction]","authors":"Rui Liu, Yajuan Chen, Tao Shou, Jing Hu, Chen Qing","doi":"10.2147/ott.s479422","DOIUrl":"https://doi.org/10.2147/ott.s479422","url":null,"abstract":"","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Therapeutic Potential of Durvalumab in Adults with Locally Advanced or Metastatic Biliary Tract Cancer: Evidence to Date","authors":"Michael Storandt, Zhaohui Jin, Amit Mahipal","doi":"10.2147/ott.s391707","DOIUrl":"https://doi.org/10.2147/ott.s391707","url":null,"abstract":"","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141033755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testosterone Exacerbates the Formation of Liver Cancer Induced by Environmental N-Nitrosamines Exposure: Potential Mechanisms and Implications for Human Health","authors":"Xin Yin, Hong-Wei Gu, Dan Ning, Yu-Sang Li, He-Bin Tang","doi":"10.2147/ott.s456746","DOIUrl":"https://doi.org/10.2147/ott.s456746","url":null,"abstract":"","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141028584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scalp Metastasis After Breast Cancer Surgery: A Case Report","authors":"Jingxuan Wu, Wenzhu Zhang, Hong Zhang, Xingjia Lu, Biqing Luan, Qizhi Yang, Liang Chen, Wenlin Chen, Fei Ge","doi":"10.2147/ott.s456532","DOIUrl":"https://doi.org/10.2147/ott.s456532","url":null,"abstract":"","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Non-Coding RNA TRG-AS1 Promoted Proliferation and Invasion of Lung Cancer Cells Through the miR-224-5p/SMAD4 Axis [Retraction]","authors":"Mengyan Zhang, Weiguo Zhu, Mansour Haeryfar, Sumei Jiang, Xiang Jiang, Wei Chen, Jiancheng Li","doi":"10.2147/ott.s474055","DOIUrl":"https://doi.org/10.2147/ott.s474055","url":null,"abstract":"Retraction for the article Long Non-Coding RNA TRG-AS1 Promoted Proliferation and Invasion of Lung Cancer Cells Through the miR-224-5p/SMAD4 Axis","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}