OncoTargets and therapy最新文献

{"title":"Downregulation of lncRNA <i>ANRIL</i> Suppresses Growth and Metastasis in Human Osteosarcoma Cells [Retraction].","authors":"","doi":"10.2147/OTT.S484228","DOIUrl":"https://doi.org/10.2147/OTT.S484228","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/OTT.S170293.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"537-538"},"PeriodicalIF":2.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Silencing of VEGF-A and Angiopoietin-2, a More Effective Way to Inhibit the Ishikawa Endometrial Cancer Cell Line [Retraction].","authors":"","doi":"10.2147/OTT.S484231","DOIUrl":"https://doi.org/10.2147/OTT.S484231","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/OTT.S194064.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"539-540"},"PeriodicalIF":2.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Sea Sponge <i>Callyspongia siphonella</i> Extract Induced Growth Inhibition and Apoptosis in Breast MCF-7 and Hepatic HepG-2 Cancer Cell Lines in 2D and 3D Cell Cultures.","authors":"Sana A Fadil, Fadwa A Aljoud, Ahmed R Yonbawi, Ahmad J Almalki, Rawan H Hareeri, Abrar Ashi, Mehal Atallah AlQriqri, Nada S Bawazir, Hadeel H Alshangiti, Lamiaa A Shaala, Diaa T A Youssef, Faris A Alkhilaiwi","doi":"10.2147/OTT.S467083","DOIUrl":"10.2147/OTT.S467083","url":null,"abstract":"<p><strong>Introduction: </strong>The increasing incidence of cancer diseases necessitates the urgent exploration of new bioactive compounds. One of the trends in drug discovery is marine sponges which is gaining significant support due to the abundant production of natural pharmaceutical compounds obtained from marine ecosystems. This study evaluates the anticancer properties of an organic extract from the Red Sea sponge <i>Callyspongia siphonella (C. siphonella)</i> on HepG-2 and MCF-7 cancer cell lines.</p><p><strong>Methods: </strong><i>C. siphonella</i> was collected, freeze-dried, and extracted using a methanol-dichloromethane mixture. The extract was analyzed via Liquid Chromatography-Mass Spectrometry. Cytotoxic effects were assessed through cell viability assays, apoptosis detection, cell cycle analysis, mitochondrial membrane potential assays, scratch-wound healing assays, and 3D cell culture assays.</p><p><strong>Results: </strong>Fifteen compounds were identified in the <i>C. siphonella</i> extract. The extract showed moderate cytotoxicity against MCF-7 and HepG-2 cells, with IC₅₀ values of 35.6 ± 6.9 μg/mL and 64.4 ± 8 μg/mL, respectively, after 48 hours of treatment. It induced cell cycle arrest at the G2/M phase in MCF-7 cells and the S phase in HepG-2 cells. Apoptosis increased significantly in both cell lines, accompanied by reduced mitochondrial membrane potential. The extract inhibited cell migration, with notable reductions after 24 and 48 hours. In 3D cell cultures, the extract had IC₅₀ values of 5.1 ± 2 μg/mL for MCF-7 and 166.4 ± 27 μg/mL for HepG-2 after 7 days of treatment, showing greater potency in MCF-7 spheres compared to HepG-2 spheres.</p><p><strong>Discussion and conclusion: </strong>The anticancer activity is attributed to the bioactive compounds. The <i>C. siphonella</i> extract's ability to induce apoptosis, disrupt mitochondrial membrane potential, and arrest the cell cycle highlights its potential as a novel anticancer agent. Additional research is required to investigate the underlying mechanism by which this extract functions as a highly effective anticancer agent.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"521-536"},"PeriodicalIF":2.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Combined Chemotherapy and Targeted Therapy on Pancreatic Neuroendocrine Carcinoma with Liver Metastasis: A Single-Center Modified Nomogram Analysis.","authors":"Wenhao Luo, Hao Chen, Taiping Zhang","doi":"10.2147/OTT.S466213","DOIUrl":"10.2147/OTT.S466213","url":null,"abstract":"<p><strong>Objective: </strong>To establish a modified nomogram model for pancreatic neuroendocrine carcinoma (pNEC) patients with liver metastasis via single-center clinical data, and to provide guidelines for improving the diagnosis and treatment of patients.</p><p><strong>Methods: </strong>A retrospective analysis of clinical data from pNEC patients with liver metastasis at Peking Union Medical College Hospital (January 2000 to November 2023) was conducted. Univariate and multivariate Cox regression analyses were employed to identify prognostic factors for overall survival (OS). Kaplan-Meier curves were generated, and a modified nomogram predictive model was developed to illustrate the prognosis of pNEC patients with liver metastasis. Calibration plots and C-index were used to validate the model's feasibility, accuracy, and reliability.</p><p><strong>Results: </strong>Forty-five participants with the rare cancer type pNEC and liver metastasis were included in the study. Kaplan-Meier curves revealed that primary tumor resection (PTR), chemotherapy or targeted therapy, and tumor size equal to or less than 5cm significantly improved OS compared to those without PTR, chemotherapy or targeted therapy, and tumor size larger than 5cm. Multivariate Cox regression analysis identified PTR, a combination of chemotherapy and targeted therapy, and tumor size as independent prognostic factors for OS. The predictive nomogram model exhibited acceptable performance with a C-index of 0.744 (0.639-0.805) through bootstrapping.</p><p><strong>Conclusion: </strong>Combining chemotherapy with targeted therapy enhances the survival of pNEC patients with liver metastasis. The modified nomogram model and predictive score table offer valuable references and insights for both clinicians and patients.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"509-519"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11204791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of MMSET Impairs Breast Cancer Proliferation and Metastasis Through Inhibiting Wnt/β-Catenin Signaling [Retraction].","authors":"","doi":"10.2147/OTT.S483240","DOIUrl":"https://doi.org/10.2147/OTT.S483240","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/OTT.S196430.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"507-508"},"PeriodicalIF":2.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11198004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Dacomitinib and Selpercatinib Treatment for a Patient with <i>EGFR</i>-Mutant Non-Small Cell Lung Cancer and Acquired <i>CCDC6-RET</i> Fusion.","authors":"Cheng-Yin Liu, Chia-Hsin Liu","doi":"10.2147/OTT.S470946","DOIUrl":"10.2147/OTT.S470946","url":null,"abstract":"<p><p><i>RET</i> rearrangements are recognized drivers in lung cancer, representing a small subset (1-2%) of non-small cell lung cancer (NSCLC). Additionally, <i>RET</i> fusions also serve as a rare acquired resistance mechanism in <i>EGFR</i>-mutant NSCLC. Only a few NSCLC cases have been reported with co-occurrence of <i>EGFR</i> mutations and <i>RET</i> fusions as an acquired resistance mechanism induced by EGFR-tyrosine kinase inhibitors (TKIs). A 68-year-old man diagnosed with lung adenocarcinoma harboring <i>EGFR</i> L858R mutation initially responded well to dacomitinib, a second-generation EGFR-tyrosine kinase inhibitor (TKI). Afterward, he developed acquired resistance accompanied by a <i>RET</i> rearrangement. Next-generation sequencing (NGS) analysis revealed that the tumor possessed both the new <i>CCDC6-RET</i> fusion and the <i>EGFR</i> L858R mutation. Subsequently, he was treated with a combination of cisplatin, pemetrexed, and bevacizumab resulting in a partial response. Nevertheless, his condition deteriorated as the disease progressed, manifesting as hydrocephalus, accompanied by altered consciousness and lower limb weakness. The subsequent combined treatment with dacomitinib and selpercatinib resulted in a significant improvement in neurological symptoms. Here, we first identified acquired <i>CCDC6-RET</i> fusion with a coexisting <i>EGFR</i> L858R mutation following dacomitinib treatment. Our findings highlight the importance of NGS for identifying <i>RET</i> fusions and suggest the potential combination of dacomitinib and selpercatinib to overcome this resistance. For NSCLC patients with <i>RET</i> rearrangements and no access to RET inhibitors, pemetrexed-based chemotherapy provides a feasible alternative.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"499-506"},"PeriodicalIF":2.7,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Clinical Benefit with Futibatinib in a Patient with FGFR Inhibitor-Pretreated <i>FGFR2</i> Fusion-Positive Intrahepatic Cholangiocarcinoma: Case Report.","authors":"Paolo D d'Arienzo, Alan R MacDonald, Virjen Patel, Yuk T Ma, Rille Pihlak, Naureen Starling","doi":"10.2147/OTT.S434449","DOIUrl":"10.2147/OTT.S434449","url":null,"abstract":"<p><p>Multiple FGFR inhibitors have demonstrated significant activity in pretreated advanced <i>FGFR2</i> fusion-positive intrahepatic cholangiocarcinoma. The irreversible pan-FGFR inhibitor futibatinib has the potential to overcome acquired resistance to ATP-competitive FGFR inhibitors in a subset of patients. We present a case of prolonged clinical benefit using FGFR inhibitors sequentially, initially an ATP-competitive inhibitor followed by futibatinib upon progression, for a total of 36 months of FGFR-targeting therapy. This case supports sequential FGFR-targeting therapies for <i>FGFR2</i> fusion-positive cholangiocarcinoma, with futibatinib acting as rescue therapy after failure of ATP-competitive inhibitors.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"17 ","pages":"489-496"},"PeriodicalIF":4.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11184230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different Role of TRF1 and TRF2 Expression in Non-Small Cell Lung Cancers","authors":"Mincheol Chae, Jae-Ho Lee, Jong Ho Park, Dong Yoon Keum, Hanna Jung, Youngok Lee, Deok Heon Lee","doi":"10.2147/ott.s461430","DOIUrl":"https://doi.org/10.2147/ott.s461430","url":null,"abstract":"<strong>Background:</strong> TRF1, TRF2, and TERT (Telomerase reverse transcriptase) are telomere-associated factors that regulate telomere length. Genetic changes in these genes may be associated with cancer pathogenesis; however, this relationship has not yet been comprehensively elucidated in lung cancer.<br/><strong>Aim:</strong> : Exploring the clinicopathologic and prognostic values of TRF1, TRF2, and TERT mRNA expression in non-small cell lung cancers (NSCLC).<br/><strong>Methods:</strong> : The clinical significance of TRF1, TRF2, and TERT expression in 141 patients with NSCLC was investigated. Additionally, these findings were supported by the open big data from The Cancer Genome Atlas (TCGA).<br/><strong>Results:</strong> : TRF1 and TRF2 expression levels tended to be associated with smoking, and TERT expression was positively correlated with age. The survival analysis showed that TRF1 expression predicted a better prognosis for squamous cell carcinoma (SCC), whereas TRF2 expression was associated with a shorter survival in adenocarcinoma. TCGA data also showed a better prognosis for SCC with TRF1 expression. However, the TRF2 results were not in agreement with our data.<br/><strong>Conclusions:</strong> : We present the clinical and prognostic values of TRF1, TRF2, and TERT expression in NSCLC tissues and TCGA. Our findings suggest that TRF1 expression is a possible prognostic marker for NSCLC, particularly SCC.<br/><br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"67 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141252973","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":"The Role and Mechanism of the Histone Methyltransferase G9a in Tumors: Update","authors":"Hangsheng Zhou, Jiandong Gui, Lijie Zhu, Yuanyuan Mi","doi":"10.2147/ott.s451108","DOIUrl":"https://doi.org/10.2147/ott.s451108","url":null,"abstract":"<strong>Abstract:</strong> Methylation-mediated gene silencing is closely related to the occurrence and development of human tumors. The euchromatic histone lysine methyltransferase 2 (EHMT2, also known as G9a) is highly expressed in many tumors and is generally considered to be an oncogene, which is associated with the poor outcome of many tumors. Combined immunotherapy and immune checkpoint blockade therapy also have good efficacy and certain safety. However, there are still many difficulties in the drugs targeting G9a, and the combined effect and safety of G9a with many drugs is still under study. This article aims to summarize the role and mechanism of G9a and its inhibitors in tumors in the past two years, and to understand the application prospect of G9a from the perspective of diagnosis and treatment.<br/><br/><strong>Keywords:</strong> cancer, G9a, methyltransferase, function, mechanism<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"76 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141188504","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":"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":"15 1","pages":""},"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}