Current cancer drug targets最新文献

{"title":"Exploration of the Values of Macrophage Differentiation-Related Genes in Prognosis and Immunotherapy Prediction for Hepatocellular Carcinoma.","authors":"Jinglu Yu, Chuting Zhang, Qiqi Tao, Zhengping Yu, Jianjian Zheng, Shanshan Hu","doi":"10.2174/0115680096423728260106145843","DOIUrl":"https://doi.org/10.2174/0115680096423728260106145843","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) poses significant global health and economic challenges, with tumor-associated macrophages (TAMs) implicated in its progression. This study aimed to develop a prognostic signature based on macrophage differentiation-related genes (MDRGs) for HCC risk stratification.</p><p><strong>Materials and methods: </strong>Transcriptomic data from HCC and adjacent tissues were analyzed to identify differentially expressed genes (DEGs). Prognostic MDRGs were screened via univariate Cox regression and refined using LASSO regression. A multivariate Cox-derived risk model was established and validated using Kaplan-Meier survival analysis. Immune infiltration and immunotherapy responses were assessed, alongside in vitro functional validation of key genes.</p><p><strong>Results: </strong>Analysis identified 67 prognostically relevant MDRGs from HCC-specific DEGs. LASSO regression and multivariate Cox analysis yielded a robust 9-MDRG signature. Patients stratified into high-risk groups exhibited significantly shorter survival, elevated macrophage infiltration, and enhanced predicted responses to anti-PD1/CTLA4 therapies. In vitro studies revealed that NCAPG, a transcription factor within the signature, promotes HCC progression by upregulating the core regulator EZH2.</p><p><strong>Discussion: </strong>The established 9-MDRG signature effectively stratifies HCC patients into distinct risk groups with significant prognostic divergence. Its strong association with heightened TAM infiltration underscores the biological relevance of macrophage differentiation in HCC progression. Crucially, the model exhibits predictive value for markers associated with immunotherapy response, suggesting high-risk patients may benefit preferentially from antiPD1/CTLA4 regimens. Furthermore, the mechanistic dissection of the NCAPG-EZH2 axis within the signature unveils a key molecular pathway linking macrophage biology to HCC aggressiveness, nominating NCAPG and EZH2 as novel therapeutic targets.</p><p><strong>Conclusion: </strong>We developed a clinically translatable 9-MDRG prognostic model that effectively predicts HCC outcomes and informs immunotherapy strategies. The identified NCAPG-EZH2 axis highlights potential therapeutic targets for macrophage-mediated HCC progression.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763977","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":"NDUFA10: An Emerging Oncogenic Driver of Metastasis in Lung Adenocarcinoma.","authors":"Tianqi Hu, Yixin Chen, Yi Lu, Yuyu He, Lunan Chou, Jiali Fu, Kate Huang, Yumin Wang, Jie Chen","doi":"10.2174/0115680096440556260123113410","DOIUrl":"https://doi.org/10.2174/0115680096440556260123113410","url":null,"abstract":"<p><strong>Introduction: </strong>mRNA sequencing analysis suggested that ubiquinone oxidoreductase subunit A10 (NDUFA10) may function as a key downstream effector of circRAPGEF5 in lung adenocarcinoma (LUAD) progression; however, the underlying mechanism remains unclear. This study aimed to explore the expression and clinical significance of NDUFA10 in LUAD cells and its role in cell proliferation and metastasis.</p><p><strong>Methods: </strong>Variations in NDUFA10 mRNA and protein expression between LUAD and adjacent normal tissues were assessed using the Cancer Genome Atlas Program (TCGA) and Tumor Immune Estimation Resource (TIMER) databases. These findings were subsequently validated in LUAD cell lines via Reverse Transcription Quantitative PCR (RT-qPCR). Further analyses included clinical correlation, Receiver Operating Characteristic (ROC), survival analysis, and Gene Set Enrichment Analysis (GSEA) of NDUFA10. The functional role of NDUFA10 was investigated in vitro at the cellular level.</p><p><strong>Results: </strong>NDUFA10 mRNA expression was significantly upregulated in pan-cancer analyses and specifically in LUAD. Its expression levels correlated with clinical parameters, including metastasis (M stage) and patient gender. Elevated NDUFA10 expression demonstrated a negative correlation with overall survival (OS) and first progression (FP), and was associated with the best efficacy of anti-PD-1/PD-L1 antibody therapies. GSEA indicated significant enrichment of NDUFA10-related genes in pathways involving WNT and Notch signaling, as well as the TGFβ pathway regulating the epithelial-mesenchymal transition (EMT). In vitro, knockdown of NDUFA10 significantly suppressed LUAD cell proliferation, colony formation, migration, and invasion compared to control cells.</p><p><strong>Discussion: </strong>This study focuses on the role of NDUFA10 in lung adenocarcinoma (LUAD). Through database screening and experimental verification, it was found that NDUFA10 is upregulated in LUAD. Its high expression is associated with advanced N stage (N2/N3), high pathological stage (III/IV), poor therapeutic effect and advanced age, suggesting its potential as a biomarker for poor diagnosis and prognosis. Further analysis indicates that NDUFA10 is associated with immune infiltration and involves pathways such as neuroactive ligand-receptor interaction and chemokine signaling. In vitro experiments have confirmed that knocking down NDUFA10 can inhibit the proliferation and metastasis of lung adenocarcinoma cells. This study provides a preliminary basis for the function and mechanism of NDUFA10 in LUAD. In the future, we will further explore how it affects tumor progression through the WNT/Notch/TGFβ pathway or ROS/ energy metabolism.</p><p><strong>Conclusion: </strong>Silencing NDUFA10 suppresses LUAD cell proliferation, migration, and invasion. The study suggested that circRAPGEF5 regulated NDUFA10 to facilitate the progression of LUAD.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627351","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":"Methyl-β-Cyclodextrin Enhances the Chemotherapeutic Efficacy of Paclitaxel in Breast Cancer Cells.","authors":"Haili Jin, Liping Zhou, Tianzhen Lin, Wenbin Chen, Ruhui Yang","doi":"10.2174/0115680096430730260120060026","DOIUrl":"https://doi.org/10.2174/0115680096430730260120060026","url":null,"abstract":"<p><strong>Background: </strong>Chemoresistance, a long-standing clinical challenge in breast cancer treatment, continues to affect chemotherapy outcomes. Cholesterol-enriched lipid rafts are increasingly recognized as key mediators of drug efflux, primarily via transporters like P-glycoprotein (P-gp). Therefore, targeting lipid rafts as a viable treatment strategy to restore cancer sensitivity to chemotherapeutics. Our study aims to evaluate whether methyl-β-cyclodextrin (MβCD), a well-characterized lipid raft disruptor, can enhance the antitumor efficacy of paclitaxel liposomes (PTX-LPs) in preclinical breast cancer models, with a particular focus on triple-negative breast cancer subtypes.</p><p><strong>Methods: </strong>The sequential effects of paclitaxel liposomes (PTX-LPs) and MβCD were evaluated in vitro in MDA-MB-231 cells with a 1-hour dosing interval. Intracellular paclitaxel retention, apoptotic rate, and the expression of Flotillin-1, Caveolin-1, and P-gp were quantified by HPLC, flow cytometry, and Western blotting. In vivo therapeutic effects were further assessed in tumor-bearing xenograft models following sequential administration with a 5-hour interval.</p><p><strong>Results: </strong>Flotillin-1 was significantly overexpressed across breast cancer subtypes. Sequential PTX-LPs and MβCD treatment significantly increased intracellular paclitaxel retention (3-fold at 48 h vs. PTX-LPs alone, p < 0.01) and apoptotic rate (38.6% vs. 16.2%, p < 0.01). Moreover, MβCD reduced the expression of Flotillin-1, Caveolin-1, and P-gp in MDA-MB231 cells. Importantly, sequential treatment achieved 73.6% tumor growth inhibition in vivo (p < 0.01 vs. PTX-LPs alone).</p><p><strong>Discussion: </strong>Breast cancer chemoresistance is closely associated with lipid rafts. Here, we demonstrate that sequential treatment with MβCD and PTX-LPs disrupts lipid rafts, suppresses efflux transporter activity, enhances intracellular paclitaxel retention, and potentiates paclitaxel efficacy in MDA-MB-231 cells. However, the long-term safety of MβCD and its applicability to other breast cancer subtypes remain to be further investigated.</p><p><strong>Conclusion: </strong>Sequential therapy with MβCD and PTX-LPs enhances the chemotherapeutic efficacy of PTX-LPs in breast cancer. This effect is mediated by the inhibition of drug efflux through the disruption of lipid raft integrity. This strategy provides a novel approach to overcoming chemoresistance.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627206","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":"Comparative Analysis of Homologous Recombination Repair Status Across Gynecologic and Breast Cancers in Chinese Populations.","authors":"Yongsheng Huang, Jiajia Shao, Xinke Yin, Yuanling Jiang, Jiahuan Luo, Jinghua Huang, Jianli Zhao, Sha Fu, Jianwei Liao","doi":"10.2174/0115680096437832251215093401","DOIUrl":"https://doi.org/10.2174/0115680096437832251215093401","url":null,"abstract":"<p><strong>Background: </strong>Homologous recombination deficiency (HRD) is a key genomic hallmark in multiple malignancies, driving genomic instability and influencing responsiveness to targeted therapies such as PARP inhibitors. While HRD has been extensively studied in cancers such as breast and ovarian carcinoma, its associations with broader genomic characteristics across diverse female-specific tumor types, including endometrial and cervical carcinoma, remain less well defined.</p><p><strong>Methods: </strong>Utilizing a 520-gene next-generation sequencing (NGS) panel, we conducted a retrospective analysis of genomic mutational profiles and HRD scores in 270 patients, including those with breast carcinoma (BRCA), ovarian carcinoma (OV), cervical carcinoma (CCA), and uterine corpus endometrial carcinoma (UCEC). Correlations between mutated genes, tumor mutation burden (TMB), microsatellite instability status, and genomic HRD scores were further analyzed.</p><p><strong>Results: </strong>BRCA, OV, and CCA exhibit comparable median HRD scores, which are significantly higher than those observed in UCEC. Within the HR gene spectrum, deficiencies in BRCA1/2 and mutations in PALB2 were associated with high HRD scores (≥42). Notably, a subset of patients without germline or somatic mutations in BRCA1/2, PALB2, or other HR-related genes also displayed high HRD. Further analysis revealed that, in BRCA, mutations in SMARCA4, EPHA5, and JAK2 may serve as potential HRD markers, whereas in OV, PIK3CA mutations could indicate a negative association. Additionally, TP53 mutations were linked to high HRD scores in BRCA, OV, and UCEC patients, while no such association was observed in CCA patients.</p><p><strong>Conclusion: </strong>The mutational patterns affecting homologous recombination repair differ across gynecologic and breast cancers. Further research into cancer-specific HRD mechanisms is warranted.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618509","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":"In Silico Multi-omics Analyses of Kinesin Family Member 15 in Pan-Cancer and Validation in Tissue Microarray.","authors":"Mengqin Xiang, Qing Hu, Yanchun Li, Hao Wu","doi":"10.2174/0115680096420482251130063549","DOIUrl":"https://doi.org/10.2174/0115680096420482251130063549","url":null,"abstract":"<p><strong>Introduction: </strong>Kinesin family member 15 (KIF15) is a molecular motor protein that participates in bipolar spindle assembly and centrosome separation during metaphase in normal cells. However, accumulating evidence has shown that KIF15 is aberrantly regulated in the state of malignancy and is associated with the progression of cancers.</p><p><strong>Materials and methods: </strong>We analyzed the mRNA expression, protein expression, single-cell gene expression, prognoses, and immune reactivities of KIF15 using the data from various sources, including the Cancer Cell Line Encyclopedia, The Cancer Genome Atlas database, the Clinical Proteomic Tumor Analysis Consortium Confirmatory/Discovery database, and Cancer Single-cell Expression Map. Additionally, immunohistochemistry was performed to validate KIF15 protein expression in human tumor samples.</p><p><strong>Results: </strong>The data from the present pan-cancer analysis elucidated that KIF15 expression was increased in more than 25 human tumors. Furthermore, it was found to be highly corre-lated with biological pathways, immune cell infiltration, and poor prognoses across multiple cancers. Additionally, tissue microarray analysis confirmed abundant cytoplasmic KIF15 expression in ovarian serous carcinoma and colorectal adenocarcinoma, with significantly higher levels compared to adjacent normal tissues.</p><p><strong>Discussion: </strong>Consistent patterns of high KIF15 expression were also evident across various cancer cell lines in the CCLE dataset. Collectively, these observations suggest KIF15 is in-timately involved in the progression of multiple human cancers. By analyzing both the pro-teins that interact with KIF15 and the genes that show correlation with its expression, KEGG pathway enrichment indicated that processes such as cell cycle regulation, gap and tight junction dynamics, involvement of microRNAs in cancer, and the p53 signaling pathway may underlie the role of KIF15 in cancer development.</p><p><strong>Conclusion: </strong>KIF15 may serve as a potential biomarker and oncogenic factor in multiple cancer types.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618487","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":"MiR-124-3p Suppresses Glioma Cells Progression by Targeting STAT3/NAMPT and Inhibiting AKT/ERK Signaling.","authors":"Yan Liu, Wei Zhao, Zhi Tang, Wenwu Liu, Lei Wang, Te Wang","doi":"10.2174/0115680096444128260128052644","DOIUrl":"https://doi.org/10.2174/0115680096444128260128052644","url":null,"abstract":"<p><strong>Background: </strong>In our preliminary study, bioinformatics analyses identified differentially expressed miRNAs and mRNAs in glioma versus peritumoral samples, with functional validation of multiple miRNA-mRNA regulatory axes. MicroRNA-124-3p (miR-124-3p)/nicotinamide phosphoribosyltransferase (NAMPT) was among these axes and may critically regulate glioma malignant phenotypes, and this study aimed to validate their regulatory interactions.</p><p><strong>Methods: </strong>We analyzed NAMPT expression in glioma tissues using clinical datasets from the Chinese Glioma Genome Atlas (CGGA). Functional effects of miR-124-3p and NAMPT were evaluated in U87 and U251 glioma cells using quantitative real-time PCR (qRT-PCR), Western blotting, colony formation assays, CCK-8 cell viability assays, Transwell invasion assays, and flow cytometry. The direct interaction between miR-124-3p and NAMPT was investigated using dual-luciferase reporter assays.</p><p><strong>Results: </strong>Clinical data revealed that elevated NAMPT expression correlated with poor prognosis, advanced pathological grade, and IDH-wild-type gliomas. MiR-124-3p overexpression significantly inhibited glioma cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, miR-124-3p downregulated NAMPT expression through regulation, leading to suppression of the p-AKT and p-ERK signaling pathways. Notably, NAMPT overexpression rescued the tumor-suppressive effects of miR-124-3p, confirming its critical role in this axis. However, dual-luciferase reporter assays ruled out a direct interaction between miR-124-3p and the NAMPT transcript, suggesting an indirect regulatory mechanism. Further investigation through WB and rescue experiments identified the transcription factor STAT3 as the key intermediary, serving as a functional bridge linking miR-124-3p to the regulation of NAMPT expression.</p><p><strong>Discussion: </strong>Accumulating evidence demonstrates that miR-124-3p functions as a potent tumor suppressor across diverse malignancies through distinct molecular mechanisms. STAT3, which is directly targeted by miR-124-3p, serves as the functional bridge linking miR-124-3p to NAMPT regulation. NAMPT, as a critical node in the NAD⁺ biosynthetic pathway, influences the malignant biological behavior of glioma through downstream PI3K/AKT and MEK/ERK signaling transduction pathways.</p><p><strong>Conclusion: </strong>MiR-124-3p functions as a tumor suppressor in glioma by repressing STAT3/NAMPT-mediated AKT/ERK signaling, highlighting its potential as a diagnostic biomarker and therapeutic target for glioma management.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618546","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":"Immunotherapy with Chemotherapy in Recurrent or Metastatic Maxillary Sinus Squamous Cell Carcinoma: A Real-world Study in China.","authors":"Shuyang Zhang, Jingyang Zhao, Yijun Shi, Changyu Zhu, Xinyu Li, Weitao Zhang, Heshu Liu, Wei Li","doi":"10.2174/0115680096443625260219081015","DOIUrl":"https://doi.org/10.2174/0115680096443625260219081015","url":null,"abstract":"<p><strong>Background: </strong>Patients with Recurrent or Metastatic Maxillary Sinus Squamous Cell Carcinoma (R/M MSSCC) generally have a poor prognosis. Traditional chemotherapy has limited efficacy. In real-world practice, there is no data about the efficacy and safety of immunotherapy combined with chemotherapy in these patients.</p><p><strong>Objective: </strong>This study aimed to evaluate the efficacy and safety of immunotherapy combined with chemotherapy for patients with unresectable R/M MSSCC in a real-world setting.</p><p><strong>Methods: </strong>We included 15 R/M MSSCC patients treated at Beijing Tongren Hospital from January 2021 to December 2024. All patients received PD-1 inhibitors combined with chemotherapy. We collected and analyzed clinical information and survival data of all patients.</p><p><strong>Results: </strong>The Objective Response Rate (ORR) was 26.7%, and the Disease Control Rate (DCR) was 86.7%. The median Progression-Free Survival (PFS) was 5.1 months (95% CI 0.26-17.27), and the median Overall Survival (OS) was 7.8 months (95% CI 0.44-10.23). Compared with patients with PD-L1 CPS < 20, patients with CPS ≥20 had a longer median PFS (14.1 months vs.3.9 months, p=0.031, HR 0.223, 95%CI 0.040-1.264). The most frequent grade 1/2 Adverse Events (AEs) included: loss of appetite (15/15, 100%), alopecia (13/15, 86%), anemia (10/15, 67%), peripheral neurotoxicity (10/15, 67%), and leukopenia (8/15, 53%). Only one person experienced a grade 4 AE, which was chemotherapy-induced neutropenia. The most common immune-related AE was hypothyroidism (3/15, 20%). No serious immune-related adverse events were observed.</p><p><strong>Discussion: </strong>This study shows that PD-1 inhibitors combined with chemotherapy are a feasible and promising treatment strategy for recurrent/metastatic MSSCC. Most importantly, the results suggest that PD-L1 CPS has predictive value in this anatomical subtype. Patients with CPS ≥20 showed a significant survival benefit.</p><p><strong>Conclusion: </strong>In real-world practice, PD-1 inhibitors combined with chemotherapy are an effective and safe treatment option for recurrent/metastatic R/M MSSCC.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618512","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":"Resistance by Inhibiting the STAT3/SLC25A27 Pathway and Promoting Ferroptosis in Hepatocellular Carcinoma.","authors":"Ranran Bi, Luyuan Ma, Ruolan Gu, Shilong Dong, Xinyang Li, Wenpeng Liu, Pengfei Zhang, Feng Gao, Chuan Shen, Caiyan Zhao","doi":"10.2174/0115680096426616260214221301","DOIUrl":"https://doi.org/10.2174/0115680096426616260214221301","url":null,"abstract":"<p><p>Lenvatinib is the first-line drug used in the systemic treatment of advanced hepatocellular carcinoma (HCC), although its therapeutic efficacy is limited by emerging resistance mechanisms. Our study aims to investigate the molecular pathways underlying lenvatinib resistance in HCC to inform circumvention strategies for therapeutic resistance. Our findings demonstrated that solute carrier family 25 member 27 (SLC25A27) is upregulated in lenvatinib-resistant (Lenva-R) HCC cells by RNA sequencing (RNA-seq). Similarly, SLC25A27 expression is higher in Lenva-R than lenvatinib-sensitive (Lenva-S) HCC cells and tissues via Quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry (IHC) in vitro and vivo. Cell Counting Kit-8 (CCK-8) assay was performed to determine cell viability. Colony formation assay was performed to determine cell proliferation capacity. DCFH-DA staining was used to detect the levels of intracellular reactive oxygen species (ROS). Observation of mitochondrial morphology by using transmission electron microscopy (TEM). The corresponding assay kits were used to analyze the levels of malondialdehyde (MDA), glutathione (GSH)/ oxidized glutathione disulfide (GSSG) ratio, and mitochondrial membrane potential (MMP). Gain- and loss-of-function experiments demonstrated that SLC25A27 promotes survival, proliferation and lenvatinib resistance in vitro. Mechanistic studies showed that SLC25A27 inhibits ferroptosis pathway via activating solute carrier family 7 member A11 (SLC7A11)/glutathione peroxidase 4 (GPX4). Dual-luciferase reporter experiments confirmed signal transducer and activator of transcription 3 (STAT3) significantly enhances SLC25A27 transcription. Moreover, artesunate promotes ferroptosis by inhibiting the STAT3/SLC25A27/ SLC7A11/GPX4 axis in vivo and in vitro. Overall, our study confirmed the combination of artesunate and lenvatinib significantly enhances the anti-HCC effect of lenvatinib, which promising therapeutic strategy to circumvent resistance in HCC.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607913","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":"miRNAs as Theragnostic Markers for PARP Inhibitor Resistance in Breast Cancer: A Systematic Review.","authors":"Mehran Molavand, Asal Golchin, Bahman Yousefi","doi":"10.2174/0115680096450856260219065705","DOIUrl":"https://doi.org/10.2174/0115680096450856260219065705","url":null,"abstract":"<p><strong>Introduction: </strong>This systematic review aims to evaluate the potential of mi-croRNAs (miRNAs) as theragnostic biomarkers for predicting resistance to PARP inhibitors in Breast Cancer (BC), highlighting their potential for personalized treatment strategies.</p><p><strong>Methods: </strong>Following PRISMA guidelines, we conducted a search in Scopus, EMBASE, Pub-Med, and Web of Science to identify studies on miRNAs as biomarkers for predicting PARP inhibitor response in BC. Articles were selected based on inclusion and exclusion criteria, focusing on in vitro and in vivo studies, with quality assessed using the SYRCLE tool and a customized checklist.</p><p><strong>Results: </strong>Seventeen studies were included, identifying 15 miRNAs with different expression patterns. Two main types of miRNA interactions with PARP inhibitors were observed: syn-ergistic and antagonistic effects, mediated through signaling pathway regulation and induc-tion of a BRCAness phenotype in DNA repair mechanisms.</p><p><strong>Discussion: </strong>The dual role of miRNAs in modulating PARP inhibitor response in BC is evi-dent. Several miRNAs, such as miR-451, miR-199a-3p, and miR-182, enhance PARP inhib-itor efficacy by targeting pathways like PI3K, BRCA1, and C/EBPβ. On the other hand, miR-181a and miR-214-5p contribute to resistance by upregulating STING and downregu-lating RAD51, respectively. These findings emphasize the complex role of miRNAs in ther-apy, highlighting their potential as both biomarkers and therapeutic targets in overcoming resistance.</p><p><strong>Conclusion: </strong>miRNAs are crucial in BC treatment with PARP inhibitors. Further clinical studies are needed to validate their roles and develop miRNA-based strategies to overcome PARP inhibitor resistance.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607846","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":"Exploration of the Synergistic Effect of Chitosan Oligosaccharide and Dacarbazine (DTIC) in the Treatment of Melanoma.","authors":"Xin Zhang, Wencui Chen, Keke Zhang, Zhende Liu, Qianqian Lyu, Liming Jin, Weizhi Liu","doi":"10.2174/0115680096423297251202110111","DOIUrl":"https://doi.org/10.2174/0115680096423297251202110111","url":null,"abstract":"<p><strong>Introduction: </strong>Dacarbazine (DTIC)-based chemotherapy remains the first-line treatment for melanoma. However, its low response rate and evident side effects limit its clinical application. The combined use of chitosan oligosaccharide (COS) and other drugs has been shown to have good anti-tumor effects. Therefore, this study aimed to investigate whether COS can be combined with DTIC for the treatment of melanoma. </p><p> Methods: By constructing a tumor-bearing model, statistical analysis of tumor size, TUNEL staining, and immunohistochemical detection of CD8, F4/80, and other indicators were conducted on tumor tissue to clarify the synergistic effect and molecular mechanism of the combination therapy. </p><p> Results: The tumor-bearing model showed that the combined use of COS-2 and DTIC resulted in a tumor inhibition rate of 82.28% and enhanced the therapeutic efficacy of DTIC in mice with melanoma. COS-2 promoted the polarization of macrophages toward the M1 type and induced tumor cell apoptosis. In addition, it remarkably enhanced monocyte-mediated phagocytosis, T-lymphocyte proliferation, and immune function, thereby attenuating inflammatory responses and reducing the side effects of DTIC. </p><p> Discussion: This study highlighted the synergistic inhibitory effects of COS-2 and DTIC on the growth of melanoma both in vitro and in vivo. Notably, COS-2 not only enhanced the anti-tumor efficacy of DTIC but also alleviated its side effects. </p><p> Conclusion: The combination therapy with COS and DTIC exhibited a synergistic effect and may be a promising therapeutic strategy for melanoma.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607560","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}