{"title":"Coumarins from <i>Citrus aurantiifolia</i> (Christm.) Swingle Peel with Potential Cytotoxic Activity Against MCF-7 Breast Cancer Cell Line: In Vitro and In Silico Studies.","authors":"Euis Julaeha, Faryanti Eka Mulyawan, Feby Marlia Anwar, Abd Wahid Rizaldi Akili, Nandang Permadi, Darwati, Dikdik Kurnia, Tati Herlina","doi":"10.2147/OTT.S506978","DOIUrl":"https://doi.org/10.2147/OTT.S506978","url":null,"abstract":"<p><strong>Aim: </strong>Breast cancer remains a prevalent and challenging health issue for women globally. In the pursuit of more effective and less harmful therapies, researchers have focused on natural compounds, especially phenolic compounds found in various plants and fruits.</p><p><strong>Purpose: </strong>This study aims to explore the potency of coumarin compounds from <i>Citrus aurantiifolia</i> (Christm.) Swingle peel as alternative treatment for breast cancer through in vitro and in silico studies.</p><p><strong>Methods: </strong>Three coumarins were isolated from <i>C. aurantiifolia</i> peel through multiple steps of column chromatograph. Their cytotoxic activities against the MCF-7 breast cancer cell line were evaluated using the MTT assay. Additionally, in silico studies, including molecular docking and molecular dynamics simulations, were conducted to evaluate the interactions of the most potent compound with estrogen receptor alpha (ERα).</p><p><strong>Results: </strong>Chemical investigation of <i>C. aurantiifolia</i> peel led to the isolation of three compounds: 5-geranyloxy-7-methoxycoumarin (1), 5-geranyloxypsoralen (2), and 8-geranyloxypsoralen (3). Cytotoxic assays revealed that compound 2 exhibited the highest cytotoxic potency against MCF-7 breast cancer cell line with an IC<sub>50</sub> of 138.51 ± 14.44 µg/mL, followed by compounds 1 and 3 with IC<sub>50</sub> values of 204.69 ± 22.91 and 478.15 ± 34.85 µg/mL, respectively. Molecular docking studies against estrogen receptor alpha (ERα) showed that 5-geranyloxypsoralen (2) had a lower docking score (-10.63 kcal/mol) compared to estradiol (-9.99 kcal/mol). Molecular dynamics simulation revealed the binding stability ERα-Compound 2 complex as evidence from the root mean square deviation (RMSD) of 2.964 ± 0.460 Å. Furthermore, pharmacokinetic predictions suggested that 5-geranyloxypsoralen may possess favourable pharmacokinetic properties, highlighting its potential as a therapeutic agent.</p><p><strong>Conclusion: </strong>The study highlights the potential of coumarin compounds from <i>C. aurantiifolia</i> peel as an alternative treatment for breast cancer, particularly 5-geranyloxypsoralen could be a promising therapeutic agent in breast cancer treatment, warranting further investigation.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"441-452"},"PeriodicalIF":2.7,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780799","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}
OncoTargets and therapyPub Date : 2025-03-29eCollection Date: 2025-01-01DOI: 10.2147/OTT.S510988
Yixuan Wang, Lianru Zhang, Yanan Du, Tingting Yan, Fang Yang, Yiqi Yang, Baorui Liu, Li Xie
{"title":"Genomic Insights Into Early Relapsed Breast Cancer: Prognostic Challenges and Mutation Landscape.","authors":"Yixuan Wang, Lianru Zhang, Yanan Du, Tingting Yan, Fang Yang, Yiqi Yang, Baorui Liu, Li Xie","doi":"10.2147/OTT.S510988","DOIUrl":"10.2147/OTT.S510988","url":null,"abstract":"<p><strong>Purpose: </strong>Early relapsed breast cancer, characterized by recurrence within two years post-surgery, often results from drug resistance and rapid progression. The clinicopathological, prognostic and molecular features of these patients still await exploration.</p><p><strong>Methods: </strong>In this study, 43 patients with early relapsed breast cancer were included as well as 42 advanced breast cancer patients who experienced a recurrence after two years since surgery as the control group. Clinicopathological factors and prognosis were compared among the two groups, and tumor tissue from 27 available early relapsed patients was subjected to genetic sequencing.</p><p><strong>Results: </strong>Compared with the control group, early relapsed group exhibited more aggressive malignant biological characteristics, shorter median overall survival (27.8 vs 49.8 months, P=0.005) and lower objective response rate for the first line treatment (42.90% vs 86.8%, P<0.001). Genetic sequencing of 27 early relapsed breast cancer demonstrated with TP53 (52%), PIK3CA (22%), and MLL3 (19%) as the top three frequently mutated genes, suggesting potential therapeutic targets for personalized treatment strategies.</p><p><strong>Conclusion: </strong>Early relapsed breast cancer patients demonstrated poor prognosis and treatment response, indicating a reagent need of effective treatment combination for disease control. Genetic sequencing may identify potential therapeutic targets, providing new therapeutic opportunities for such patients. These findings underline the urgent need for personalized therapeutic strategies informed by genetic profiling to improve outcomes for early-relapsed breast cancer patients.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"429-439"},"PeriodicalIF":2.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772815","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}
OncoTargets and therapyPub Date : 2025-03-29eCollection Date: 2025-01-01DOI: 10.2147/OTT.S509625
Yong Zhang, Hengliang Sun, Weibo Bo, Zhongwu An, Jing Li
{"title":"Integrating Bulk and Single-Cell RNA Sequencing Data Reveals the Prognostic Significance of HOXC9-Related Immune Gene Signatures in Hepatocellular Carcinoma.","authors":"Yong Zhang, Hengliang Sun, Weibo Bo, Zhongwu An, Jing Li","doi":"10.2147/OTT.S509625","DOIUrl":"10.2147/OTT.S509625","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to integrate bulk and single-cell RNA sequencing data to construct a risk score model based on HOXC9-related immune genes (HRIGs) and evaluate its prognostic value in hepatocellular carcinoma (HCC).</p><p><strong>Materials and methods: </strong>RNA sequencing data and clinical information of HCC were obtained from TCGA and GEO databases. HRIGs were identified and a risk score model was constructed using LASSO-Cox regression analysis. The association between the risk score and tumor microenvironment was analyzed using CIBERSORT and ESTIMATE algorithms. Single-cell RNA sequencing (scRNA-seq) data were used to assess cell type distribution. Cell experiments were conducted to verify the effects of HOXC9 knockdown on HCC cell proliferation and invasion.</p><p><strong>Results: </strong>HOXC9 is highly expressed in HCC and associated with poor prognosis (p=0.031). The risk score model based on four HRIGs (EGLN3, IMPDH1, LPCAT1, and MARCKSL1) showed good prognostic discrimination in both TCGA and GEO cohorts, with significantly lower overall survival in the high-risk group (p<0.0001). The high-risk group exhibited higher immune scores and increased immune cell infiltration, as well as elevated immune checkpoint expression. scRNA-seq revealed increased hepatocytes and fibroblasts but decreased T/NK cells in HCC tissues. HOXC9 knockdown significantly inhibited HCC cell proliferation and invasion.</p><p><strong>Conclusion: </strong>HOXC9 is overexpressed in HCC and correlates with poor prognosis. The HRIG-based risk score model effectively evaluates the prognosis and immune response in HCC patients, providing new insights for risk assessment and immunotherapy prediction.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"453-465"},"PeriodicalIF":2.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772818","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":"PCSK9 Manipulates Lipid Metabolism and the Immune Microenvironment in Cancer.","authors":"Chaochu Cui, Aiwei Yan, Shengming Huang, Yifan Chen, Jinyu Zhao, Cixia Li, Xianwei Wang, Jianbo Yang","doi":"10.2147/OTT.S504637","DOIUrl":"10.2147/OTT.S504637","url":null,"abstract":"<p><p>Cancer remains the foremost cause of mortality on a global scale. Immunotherapy has yielded remarkable outcomes in the fight against cancer and is regarded as one of the most crucial and promising therapeutic modalities. PCSK9, a critical target for plasma lipids control, has been extensively and deeply studied in multiple diseases. Currently, the functions of PCSK9 in cancer, particularly its immunomodulatory role, have been progressively revealed. PCSK9 is capable of modulating a variety of immune response throughout tumor progression by orchestrating lipid metabolism. Moreover, PCSK9 governs the cell fate of diverse immune cells, such as inflammatory factor signals, MHC signals, and TCR signals. This review comprehensively summarizes the current state of knowledge regarding the role and underlying mechanisms of PCSK9 in tumorigenesis, progression, immune escape, and drug resistance.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"411-427"},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753914","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":"Prognostic and Immunological Significance of NMNAT1 in Colorectal and Pan-Cancer Contexts.","authors":"Liang Wen, Ping Wang, Guosheng Zhang, Yongli Ma, Jinghui Li, Dengzhuo Chen, Linfeng Liu, Hongkai Hu, Chengzhi Huang, Xueqing Yao","doi":"10.2147/OTT.S504668","DOIUrl":"10.2147/OTT.S504668","url":null,"abstract":"<p><strong>Introduction: </strong>Nicotinamide plays a critical role in the prevention and treatment of tumors, and its metabolism is closely associated with tumor progression. The aim of this study was to understand the prognostic and immunological significance of nicotinamide metabolism-related genes in pan-cancer.</p><p><strong>Methods: </strong>We downloaded The Cancer Genome Atlas and Genotype Tissue Expression pan-cancer datasets for NMNAT1 from the UCSC database. We analyzed the differential expression, prognosis, genetic alterations, DNA methylation, immune infiltration, and co-expression with RNA modification-related genes and immune checkpoint-related genes. Genes with expression patterns similar to NMNAT1 were identified using the GEPIA library. The GSCA database was used to investigate the correlation between gene expression and drug sensitivity, as assessed by GDSC and CTRP. The CancerSEA database was employed to examine the association of NMNAT1 expression at the single-cell level across different tumors and its relation to 14 functional states. Immunohistochemistry was performed to assess the clinical significance of NMNAT1 expression.</p><p><strong>Results: </strong>NMNAT1 exhibited differential expression across 25 tumor types, including colorectal cancer (CRC), and its expression was significantly associated with the prognosis of 11 tumors. Furthermore, NMNAT1 expression correlated significantly with clinicopathological features. NMNAT1 was strongly associated with immune cells, RNA modification-related genes, and immune checkpoint-related genes in most tumors, affecting immune responses. The expression of NMNAT1 also correlated with sensitivity and resistance to several drugs. Single-cell analysis revealed that NMNAT1 is involved in the progression of retinoblastoma, uveal melanoma, and CRC. Immunohistochemical analysis confirmed that NMNAT1 expression is an independent prognostic factor in patients with CRC.</p><p><strong>Conclusion: </strong>NMNAT1 is a crucial prognostic and immune marker gene for nicotinamide metabolism, particularly in CRC. It has potential as a clinical biomarker and a therapeutic target for cancer treatment.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"389-410"},"PeriodicalIF":2.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753956","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":"Clinical Impact of Osimertinib Dose Reduction in the First-Line Setting on EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Retrospective Monocentric Study.","authors":"Hirokazu Iso, Makiko Yomota, Yukari Shirakura, Tadatsugu Yoshinaga, Shoko Kawai, Kosuke Narita, Masahiro Seike, Yukio Hosomi","doi":"10.2147/OTT.S494112","DOIUrl":"10.2147/OTT.S494112","url":null,"abstract":"<p><strong>Purpose: </strong>Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. In the FLAURA trial, osimertinib demonstrated longer progression-free survival (PFS) and overall survival (OS) compared to gefitinib or erlotinib. In the trial, dose reductions occurred in 5% of patients, primarily due to QT prolongation. However, various adverse events can also lead to dose reductions in clinical practice, and the efficacy of osimertinib after dose reduction remains unclear. The present study was conducted to evaluate the clinical impact of osimertinib dose reduction.</p><p><strong>Patients and methods: </strong>This monocentric retrospective study was conducted at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. Ninety patients with EGFR mutation-positive non-squamous non-small-cell lung cancer receiving osimertinib as their first-line therapy between August 2018 and December 2021 were included.</p><p><strong>Results: </strong>Of the cohort, 23 patients had an osimertinib dose reduction during their clinical course. The dose reduction group tended to have a lower median body weight and a higher proportion of elderly patients aged 80 years or older. The median PFS was 21.2 months (95% confidence interval [CI]: 8.22-34.18) in the dose reduction group and 18.6 (95% CI: 13.04-24.23) months in the regular-dose group. The median OS was 29.6 months (95% CI: 17.44-41.70) in the osimertinib dose-reduction group and 37.7 (95% CI: 27.10-48.23) months in the regular-dose group. Dose reduction did not significantly impact the time-dependent hazard ratio (HR) for PFS (HR 1.22 [95% CI: 0.55-1.89]) or OS (HR: 1.24 [95% CI: 0.64-2.42]). The adverse events leading to dose reduction were mainly rash, anorexia, and paronychia, and no fatal adverse events were observed after dose reduction.</p><p><strong>Conclusion: </strong>The present study suggests that dose reduction may not compromise the efficacy of osimertinib. However, the clinical impact of dose reduction is not fully understood. Physicians should carefully weigh its benefits and risks before implementation.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"379-387"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692876","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}
OncoTargets and therapyPub Date : 2025-03-17eCollection Date: 2025-01-01DOI: 10.2147/OTT.S494899
Asim Farooq, Aatif Amin, Shaarif Bashir, Merium Fatima, Muhammad Hassan, Ali Zafar Sheikh, Muhammad Tahseen, Umer Nisar Sheikh, Kashif Asghar
{"title":"Evaluation of Indoleamine 2,3-Dioxygenase (IDO) Expression in Osteosarcoma: Insights From a 10-Year Retrospective Cohort.","authors":"Asim Farooq, Aatif Amin, Shaarif Bashir, Merium Fatima, Muhammad Hassan, Ali Zafar Sheikh, Muhammad Tahseen, Umer Nisar Sheikh, Kashif Asghar","doi":"10.2147/OTT.S494899","DOIUrl":"10.2147/OTT.S494899","url":null,"abstract":"<p><strong>Introduction: </strong>Osteosarcoma, a prevalent bone malignancy in children and adolescents, is currently treated through surgical resection and chemotherapy. Advancements in cancer research are targeting immune checkpoint molecules, such as indoleamine 2,3-dioxygenase, to advance the development of immunotherapy. However, the scarcity of research on IDO in osteosarcoma results in an absence of comprehensive data, highlighting the conflicting findings surrounding IDO's role in various cancers. Our study aims to explore IDO expression in primary tumors and metastatic lesions among osteosarcoma patients, investigating its association with clinicopathological characteristics and assessing its impact on survival outcomes.</p><p><strong>Methods: </strong>150 patients diagnosed with osteosarcoma were selected between 2009 and 2019 from the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. FFPE tissue samples of primary tumors and metastatic lesions were retrieved to conduct immunohistochemical analysis. Moreover, the clinicopathological data of these patients were gathered from the hospital information system.</p><p><strong>Results: </strong>Out of 150 patients, primary tumors were accessible for 134 individuals, while metastatic lesions were available for 49 patients. IDO expression was identified in 9 (6.71%) primary tumors and 2 (4.08%) metastatic lesions among osteosarcoma patients. Furthermore, 3 patients exhibited high expression (27.3%), while 8 displayed low IDO expression (72.7%).</p><p><strong>Conclusion: </strong>Our comprehensive study findings indicate that most osteosarcoma patients do not exhibit expression of IDO. This absence of expression aligns with the characteristic \"cold\" tumor microenvironment observed in osteosarcoma. Further investigations are imperative to provide deeper insights into the intricacies of this immunomodulatory factor in the context of osteosarcoma.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"367-377"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692882","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":"Multi-Omics Analysis Revealed That TAOK1 Can Be Used as a Prognostic Marker and Target in a Variety of Tumors, Especially in Cervical Cancer.","authors":"Li Ning, Xiu Li, Yating Xu, Yu Si, Hongting Zhao, Qingling Ren","doi":"10.2147/OTT.S506582","DOIUrl":"10.2147/OTT.S506582","url":null,"abstract":"<p><strong>Background: </strong>Thousand and One Kinase 1 (TAOK1), a member of the MAPK kinase family, plays a crucial role in processes like microtubule dynamics, DNA damage response, and neurodevelopment. While TAOK1 is linked to tumorigenesis, its oncogenic role across cancers remains unclear. This study aims to explore the relationship between TAOK1 expression, prognosis, and immune function in various cancers.</p><p><strong>Methods: </strong>We analyzed TAOK1 expression in multiple cancers using TCGA, GEO, CCLE, and other bioinformatics databases. The correlation between TAOK1 expression and immune cell infiltration was assessed with the ESTIMATE algorithm. We also examined associations with tumor stemness, DNA methylation, gene copy number alterations, and drug sensitivity. The oncogenic role of TAOK1 was further evaluated in vitro with SiHa and A2780 cells and in vivo with TAOK1 overexpression in SiHa cells.</p><p><strong>Results: </strong>TAOK1 is a key prognostic biomarker in various cancers and its high expression is associated with poor prognosis. It showed a significant negative correlation with immune cell infiltration and immune checkpoints. GSEA identified its involvement in key tumour pathways, highlighting the therapeutic potential of inhibiting the TAOK1 gene. The high expression of TAOK1 is associated with DNA methylation and gene copy number variation, and in addition its upstream regulator, EP300, is closely associated with TAOK1 expression. In vitro cellular experiments demonstrated that inhibition of TAOK1 reduced the proliferation of SiHa and A2780 cells, whereas overexpression of TAOK1 in SiHa cells promoted growth. These findings were further validated in vivo by nude mouse tumourigenicity assay and human tissue immunohistochemistry.</p><p><strong>Conclusion: </strong>TAOK1 serves as a promising prognostic biomarker and potential therapeutic target, especially for cervical cancer. These results support its clinical potential in cancer prognosis and treatment strategies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"335-353"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663803","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}
OncoTargets and therapyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.2147/OTT.S486400
Rafael Cerón Maldonado, Adolfo Martínez Tovar, Christian Omar Ramos Peñafiel, Adrián De la Cruz Rosas, Anel Irais García Laguna, Iveth Mendoza Salas, Carlos Martínez Murillo, Gilberto Israel Barranco Lampón, Efreen Horacio Montaño Figueroa, Silvia Jiménez-Morales, Irma Olarte Carrillo
{"title":"<i>CYP3A5</i> Polymorphism in Circulating Tumor Cells Confers an Increased Disease-Free Survival in DLBCL Patients Treated with R-CHOP.","authors":"Rafael Cerón Maldonado, Adolfo Martínez Tovar, Christian Omar Ramos Peñafiel, Adrián De la Cruz Rosas, Anel Irais García Laguna, Iveth Mendoza Salas, Carlos Martínez Murillo, Gilberto Israel Barranco Lampón, Efreen Horacio Montaño Figueroa, Silvia Jiménez-Morales, Irma Olarte Carrillo","doi":"10.2147/OTT.S486400","DOIUrl":"10.2147/OTT.S486400","url":null,"abstract":"<p><strong>Purpose: </strong>Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous aggressive lymphoid neoplasm. Cases of refractoriness and relapse persist in approximately 40% of patients treated with first-line R-CHOP regimen, thus, the identification of factors associated with disease progression have become a necessity. Diverse polymorphisms in genes encoding proteins involved in the metabolism and elimination of chemotherapeutic drugs have been studied as potential causes of treatment failure. In oncology, liquid biopsies have emerged as a non-invasive method for detecting circulating biomarkers, thereby strengthening both diagnosis and prognosis for patients. Therefore, the purpose of this study was to determine polymorphisms in Circulating Tumor Cells (CTCs) to describe the relevance of liquid biopsy in the clinical outcomes of patients with DLBCL.</p><p><strong>Patients and methods: </strong>We analyzed 102 liquid biopsies of peripheral blood from DLBCL patients, of which CTCs were isolated by density gradient and CD20 immunomagnetic antibodies. Allelic discrimination assays were performed to analyze <i>ABCB1 C3435T, ABCG2 C421A</i> and <i>CYP3A5 A6986G</i> polymorphisms. Overall survival (OS) and disease-free survival (DFS) analysis were performed using Kaplan-Meier curves and risk analysis was performed using Cox regression.</p><p><strong>Results: </strong>We found that GG genotype of <i>CYP3A5 A6986G</i> was associated with a longer DFS (68.6% vs 49%, p=0.019) and lower risk of course with adverse event related to disease (progression, relapse and death) (OR 0.374, CI 0.187-0.745, p=0.011). No significant associations were found between <i>ABCB1 C3435T</i> and <i>ABCG2 C421A</i> genotype with the clinical outcome.</p><p><strong>Conclusion: </strong>In this study, we demonstrated that in CTCs derived from liquid biopsies, the GG genotype in the <i>CYP3A5 A6986G</i>, which is related to the metabolism and elimination of chemotherapy drugs, impacts in longer DFS. These findings confirm the relevance of circulating biomarkers in non-invasive biological samples for strengthening the prognosis of DLBCL.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"355-366"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663703","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}
OncoTargets and therapyPub Date : 2025-03-10eCollection Date: 2025-01-01DOI: 10.2147/OTT.S504279
JiaQi Liu, Jun Chu
{"title":"Comprehensive Treatment of Anaplastic Thyroid Cancer: A Case Report.","authors":"JiaQi Liu, Jun Chu","doi":"10.2147/OTT.S504279","DOIUrl":"https://doi.org/10.2147/OTT.S504279","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic thyroid cancer (ATC) is a rare, highly aggressive malignancy that accounts for less than 2% of thyroid cancers but contributes significantly to morbidity and mortality. Despite its rapid progression and poor prognosis, recent advances in targeted therapies and immunotherapies offer some hope for treatment.</p><p><strong>Case presentation: </strong>A 55-year-old female with no prior thyroid disease was diagnosed with advanced ATC after a routine check-up revealed a neck mass. She presented with a tumor compressing the trachea, recurrent laryngeal nerve, and carotid sinus, accompanied by Horner's syndrome. Fine-needle aspiration confirmed anaplastic sarcoma. After a multidisciplinary consultation, the patient was treated with anlotinib, tislelizumab, and albumin-bound paclitaxel, resulting in significant tumor shrinkage and symptomatic relief. However, due to financial constraints, treatment was discontinued. One month later, the tumor rapidly progressed, leading to tracheal compression and asphyxiation, causing her death.</p><p><strong>Conclusion: </strong>This case highlights the potential benefits of combination therapy for advanced ATC, demonstrating significant temporary improvements. However, the discontinuation of treatment due to financial limitations led to rapid disease progression, underscoring the importance of continuous, accessible care. This case also emphasizes the impact of socio-economic factors on patient outcomes and survival in aggressive cancers.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"325-333"},"PeriodicalIF":2.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649721","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}