Current cancer drug targets最新文献

{"title":"Distinct Patterns and Earlier Onset of Adverse Events in Young vs. Non-Young Breast Cancer Patients: A Real-World Analysis.","authors":"Yongxin Li, Zijun Zhu, Jiatong Lu, Yan Li, Guoshuang Shen, Jiuda Zhao","doi":"10.2174/0115680096510085261008045702","DOIUrl":"https://doi.org/10.2174/0115680096510085261008045702","url":null,"abstract":"<p><strong>Introduction: </strong>Age-related differences in Adverse Event (AE) reporting and reported Time to Onset (TTO) during systemic breast cancer treatment remain poorly characterized.</p><p><strong>Methods: </strong>We analyzed deduplicated reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 through December 2024. Reports involving systemic antineoplastic therapy were classified as Young Breast Cancer (YBC; <40 years) or Non-Young Breast Cancer (NYBC; ≥40 years). Analyses included covariate-adjusted logistic regression, 1:1 propensity-score matching, alternative age cutoffs, treatment-context sensitivity analyses, and adjusted bootstrap median regression. Multiplicity was controlled using Bonferroni correction.</p><p><strong>Results: </strong>Among 71,426 reports (YBC, 4,292; NYBC, 67,134), adjusted reporting odds differed for 10 System Organ Classes (SOCs) and 6 Preferred Terms (PTs); four SOC and four PT associations remained after matching. Unadjusted reported TTO was shorter for 5 SOCs and 8 PTs in YBC. After adjustment, only gastrointestinal disorders (-4.23 days; 95% CI, -7.11 to -1.34) and pyrexia (-5.22 days; 95% CI, -8.79 to -1.65) remained significant. Findings varied across age definitions and treatment contexts.</p><p><strong>Discussion: </strong>This is the first study to systematically characterize AE reporting patterns in YBC through an integrated pharmacovigilance framework. Using FAERS data, we compared YBC and NYBC in terms of reported AE timing and adjusted reporting odds across SOC and PT levels.</p><p><strong>Conclusion: </strong>Selected AE reporting patterns differed by age, whereas most reported-TTO differences attenuated after adjustment. These exploratory reporting associations do not establish incidence, comparative toxicity, biological onset, or causality and require confirmation in datasets with exposure denominators and detailed treatment information.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219996","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":"Single-Cell Transcriptomics Identifies Fibroblast-Associated Transcriptional Patterns and Candidate Therapeutic Targets in the Comorbidity of Non-Small Cell Lung Cancer and Obesity.","authors":"Jianxu Yuan, Shengjie Yu, Ji Zheng","doi":"10.2174/0115680096497180260909094944","DOIUrl":"https://doi.org/10.2174/0115680096497180260909094944","url":null,"abstract":"<p><strong>Background/introduction: </strong>Obesity acts as a critical modifiable risk factor for non-small cell lung cancer (NSCLC), while the key cellular and molecular drivers mediating their comorbid association remain poorly defined. Single-cell RNA sequencing (scRNA-seq) enables precise resolution of cell-specific transcriptomic features, making it an optimal tool for uncovering inter-disease regulatory patterns.</p><p><strong>Materials and methods: </strong>scRNA-seq datasets for NSCLC (GSE198099, 2 tumor/2 normal samples) and obesity (GSE214982, 5 obese/4 lean samples) were obtained from GEO and processed using Seurat (v5.x). Cell types were annotated by SingleR and validated with canonical lineage markers. Intercellular communication was inferred using CellChat (v2.x) with the human ligand-receptor database. Shared differentially expressed genes (DEGs) were identified and validated by bulk RNA-seq (GSE21933 and GSE55200). Functional enrichment, protein-protein interaction network, and drug-gene interaction analyses were integrated to identify repurposable FDA-approved agents.</p><p><strong>Results: </strong>Common cell remodeling patterns were observed across both diseases. Cell-cell communication analysis revealed that fibroblasts exhibited prominent outgoing and incoming signaling in both NSCLC and obese adipose tissues, predominantly through collagen, fibronectin, and CXCL12 pathways that target endothelial and immune cells. A total of 160 upregulated and 494 downregulated shared DEGs were identified; after stringent bulk RNA-seq validation, nine high-confidence candidates were retained, including CALCRL, NPR1, and TMEM100. These genes were enriched in endothelial differentiation, cell adhesion, and inflammatory signaling cascades.</p><p><strong>Discussion: </strong>The shared transcriptional features may point to a conserved stromal-vascular remodeling axis underlying the epidemiological link between obesity and NSCLC. The fibroblast-centered signaling patterns observed in both tissues suggest a common microenvironmental response, though functional studies are required to establish causality.</p><p><strong>Conclusion: </strong>This dual scRNA-seq-based analysis suggests that fibroblasts may function as a conserved signaling hub and highlights 9 candidate genes and several FDA-approved agents warranting further functional validation for comorbidity management in obesity- associated NSCLC.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180099","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":"Hypoxia-Responsive Co-Loaded Liposomal Drug Delivery System for the Treatment of Breast Cancer.","authors":"Harshita Singhai, Sunny Rathee, Sarjana Raikwar, Pooja Das Bidla, Shivani Saraf, Sanjay K Jain","doi":"10.2174/0115680096474148261006093302","DOIUrl":"https://doi.org/10.2174/0115680096474148261006093302","url":null,"abstract":"<p><strong>Aim: </strong>A hypoxia-responsive drug-loaded liposomal drug delivery system was designed with the aim of effective treatment of breast cancer. This involves the synthesis and characterization of a nitroimidazole derivative incorporated within the optimized nanoprobe co-loaded with berberine and doxorubicin.</p><p><strong>Background: </strong>Breast cancer is a major global health burden, demanding innovative therapeutic strategies to improve treatment modalities with minimal adverse effects. Although conventional chemotherapy is effective to some extent, it remains constrained by limited specificity, systemic toxicity, and undesirable side effects. These limitations can be addressed by spatiotemporal targeted drug delivery with minimal contact with healthy cells.</p><p><strong>Purpose: </strong></p><p><strong>Objective: </strong>The key objective of this study is to design a delivery system releasing the drug only in response to nitroreductase enzymes overexpressed in an altered hypoxic tumor microenvironment. This favors targeted drug release, tailoring breast cancer treatment.</p><p><strong>Methods: </strong>The nitroimidazole derivative was synthesized by a one-step nucleophilic substitution reaction, which was further characterized by FTIR and 1H NMR spectroscopy. The liposomal formulations consisting of plain, PEGylated, and hypoxia-responsive liposomes were optimized using a Box-Behnken design with the aim of achieving the desired vesicle size and entrapment efficiency of berberine and doxorubicin. The liposomal formulations were prepared using DPPC, DMPC, DSPE-PEG2000, and cholesterol, which were further characterized by physicochemical evaluation. In addition, sodium dithionite was used to evaluate the hypoxia-responsive structural distortion releasing the drug. The formulations were further assessed for hemolytic toxicity and cytotoxicity assays against MDA-MB-231 breast cancer cells.</p><p><strong>Results: </strong>The hypoxia-responsive derivative was successfully synthesized and characterized, affirming its suitability for the desired response. Liposomal formulations incorporating this nitroimidazole derivative met the desired standards, demonstrating optimal physicochemical characteristics. Notably, hypoxia-triggered drug release demonstrated a significant burst release under an induced hypoxic tumor microenvironment, with minimal hemolytic toxicity and superior cytotoxicity against the MDA-MB-231 breast cancer cell line compared to free drugs and other prepared liposomal formulations.</p><p><strong>Conclusion: </strong>These findings suggest that hypoxia-responsive co-loaded liposomal drug delivery systems offer a promising approach for targeted therapy, enhancing efficacy with reduced systemic side effects.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180089","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":"Evolving Molecular Drug Targets in Pancreatic Cancer: An Updated Review.","authors":"Wei Ming Pang, Xui Zie Chiam, Wei Meng Lim, Chun-Wai Mai, Zi Ni Ngai, Rhun Yian Koh","doi":"10.2174/0115680096481382261002063656","DOIUrl":"https://doi.org/10.2174/0115680096481382261002063656","url":null,"abstract":"<p><p>Pancreatic Cancer (PC) remains one of the most aggressive and lethal malignancies with an extremely low survival rate. Existing conventional therapies such as surgery, chemotherapy, radiotherapy, and immunotherapy have demonstrated limited effectiveness in significantly improving overall survival outcomes, largely due to the unique and hostile Tumour Microenvironment (TME) of PC. The TME is characterised by a desmoplastic stroma, an immunosuppressive, hypovascular, and hypoxic microenvironment, which collectively contribute to therapeutic failure. These features not only limit effective drug delivery but also promote tumour progression and treatment resistance. In recent years, the emergence of molecular targeted therapies has enabled the targeting of aberrantly activated kinases or other highly expressed targets in PC, such as KRAS, CDKN2A, TP53, SMAD4, epigenetic regulators, and signalling pathways. However, the clinical efficacy of many targeted agents remains limited, highlighting the complexity of tumour heterogeneity and adaptive resistance mechanisms. These limitations underscore the need to develop more effective therapeutic strategies for PC. Advances in precision oncology, immunotherapy, and patient derived models offer promising opportunities to improve the understanding of tumour biology, elucidate mechanisms underlying therapeutic response and resistance, and identify novel treatment strategies tailored to individual patients. Herein, this review aims to provide an updated overview of the current state of molecular therapies and the underlying molecular mechanisms and oncogenic pathways that contribute to PC initiation, development, progression and metastasis.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180094","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":"Neurotransmitters and Drug Repurposing in Cancer Therapy: Targeting the Nervous System for Tumor Suppression.","authors":"Pallavi Kumari, Sanjay Kumar","doi":"10.2174/0115680096496235261002093852","DOIUrl":"https://doi.org/10.2174/0115680096496235261002093852","url":null,"abstract":"<p><p>Emerging research indicates that the nervous system plays a complex role in cancer, with neurotransmitters regulating tumour growth, immune evasion, and resistance to therapy. It has been reported that several important oncogenic pathways are modulated by neurotransmitters, including dopamine, serotonin, norepinephrine, and glutamate, thereby governing cell proliferation, angiogenesis, and immune regulation in the tumor microenvironment. This has created new opportunities for therapeutic intervention, particularly drug-repurposing strategies that target neurotransmitter signalling. Previous reports have suggested that various neurons can promote the progression of different tumors through neuropeptide receptors, which may represent a potential drug target. Numerous FDA-approved drugs that target neurotransmitter receptors-ranging from dopamine agonists and beta-blockers to Selective Serotonin Reuptake Inhibitors (SSRIs)-have shown potential anti-cancer activity by modulating tumor-supportive neural signalling. This narrative review synthesizes current literature on the neurobiology of cancer, with an emphasis on the mechanistic roles of dopamine, serotonin, and norepinephrine/epinephrine in tumorigenesis. It further examines the repurposing of neuroactive drugs-dopamine agonists, SSRIs, tricyclic antidepressants, antipsychotics, benzodiazepines, and beta- blockers-for cancer therapy, and discusses the more limited evidence on glutamate, acetylcholine, and GABA signalling in tumor biology.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165212","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":"Supplementation with Akkermansia muciniphila Enhances the αPD-1 Efficacy in Mice Transplanted with Gut Microbiota from Patients with Colorectal Cancer.","authors":"Wei Zhao, Dan Yan","doi":"10.2174/0115680096507014261001062033","DOIUrl":"https://doi.org/10.2174/0115680096507014261001062033","url":null,"abstract":"<p><strong>Introduction: </strong>The resistance of colorectal cancer (CRC) to PD-1 blockade has positioned it as a critical focus of global research efforts. The gut microbiota is a key regulator of anti-tumor immunity, but research on bacteria that are clearly associated with primary resistance to PD-1 blockade in colorectal cancer remains incomplete.</p><p><strong>Methods: </strong>In this study, C57BL/6 mice were subjected to antibiotic pretreatment to deplete endogenous gut microbiota. The mice were then gavaged with fecal suspensions from treatment-naïve CRC patients or healthy donors, subsequently implanted with MC38 tumor cells to establish the tumor model, and then treated with the drug. Gut microbial composition was analyzed by 16S rRNA sequencing, while tumor-infiltrating immune cells and cytokine profiles were characterized using flow cytometry and immunohistochemistry, respectively.</p><p><strong>Results: </strong>CRC patient microbiota conferred resistance to anti-PD-1 therapy in mice, an effect completely reversed by oral Akkermansia muciniphila (Akk). Mechanistically, Akk reconfigured the tumor immune microenvironment, leading to a substantial increase in CD8+ T cell infiltration and function. Crucially, this potent local anti-tumor immunity was achieved without systemic immune activation.</p><p><strong>Discussion: </strong>In summary, this study establishes that Akk amplifies the local CD8⁺ T cell response, sensitizing tumors to anti-PD-1 therapy, without inducing a systemic inflammatory response.</p><p><strong>Conclusion: </strong>These findings position Akk supplementation as a promising, targeted strategy to overcome PD-1 immunotherapy resistance of MSS-CRC with a favorable safety profile.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165300","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":"Translational Horizons in Targeted Oncology: Mechanistic Insights, Therapeutic Innovations, and Clinical Impact.","authors":"Hardha Balachandran, Gowramma Byran, Senthilkumar Murugesan, Veera Venkata Karri Sathya Narayana Reddy Karri, Dipen Purohit, Kalirajan Rajagopal","doi":"10.2174/0115680096476681260927132043","DOIUrl":"https://doi.org/10.2174/0115680096476681260927132043","url":null,"abstract":"<p><strong>Introduction: </strong>Because of the elevated prevalence and death rates of cancers such as breast, lung, colorectal, bladder, gastrointestinal, and liver malignancies, cancer remains an important global health issue. More productive, targeted, and personalized therapeutic treatments are crucial, as evidenced by the growing load on the healthcare system.</p><p><strong>Materials and methods: </strong>A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify studies on molecular mechanisms and targeted therapies in oncology. Peer-reviewed articles published in English between 2015 and 2026 were screened, focusing on genomic, transcriptomic, and signalling pathway alterations across multiple cancer types.</p><p><strong>Results: </strong>The reviewed literature highlights the identification of specific protein targets that have facilitated the development of precision therapies tailored to the molecular characteristics of individual tumors. Evidence from preclinical and clinical studies indicates that these targeted approaches are associated with improved therapeutic efficacy, enhanced treatment consistency, and reduced adverse effects compared with conventional treatment modalities.</p><p><strong>Discussion: </strong>Since they allow for tailored regimens, targeted cancer treatments are a significant advancement in chemotherapy. However, issues such as drug resistance, tumour diversity, and difficulties in adopting patented breakthroughs into medical care continue to be primary barriers to their widespread utilization.</p><p><strong>Conclusion: </strong>The identification of new molecular targets and the growth of personalized therapies for cancer depend on current studies. It is believed that new advances in molecular science will contribute to the development of innovative and successful methods for therapy, and eventually decrease the prevalence of malignancies worldwide.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135435","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":"Barrier Function and Tight Junctions in Tyrosine Kinase Inhibitor-Induced Diarrhoea: A Scoping Review.","authors":"Nurul Fathiah Hairul Anuar, Amirah Abdul Rahman, Mohammad Johari Ibahim, Awla Mohd Azraai, Joanne Bowen, Wan Nor I'zzah Wan Mohamad Zain","doi":"10.2174/0115680096498489260907114046","DOIUrl":"https://doi.org/10.2174/0115680096498489260907114046","url":null,"abstract":"<p><strong>Introduction: </strong>Tyrosine Kinase Inhibitors (TKIs) are widely used in modern cancer treatment and have significantly improved outcomes for many patients. However, their use is frequently limited by gastrointestinal side effects, particularly diarrhoea. Although diarrhoea may appear mild in otherwise healthy individuals, it can substantially impair the quality of life of cancer patients and disrupt treatment continuity. In more severe cases, high-grade diarrhoea may lead to dehydration, malabsorption, fatigue and treatment interruption.</p><p><strong>Methods: </strong>This scoping review systematically synthesised available evidence examining the relationship between TKI exposure, Tight Junction Protein (TJP) alterations and diarrhoeal outcomes. Studies were identified through structured database searches and analysed descriptively according to TKI class, experimental model and reported barrier-targeted interventions.</p><p><strong>Results: </strong>Eight eligible studies were included.</p><p><strong>Discussion: </strong>Most evidence derived from preclinical models and demonstrated alterations in key TJPs, particularly ZO-1 and occludin, following exposure to selected TKIs. Irreversible pan-ErbB inhibitors, such as afatinib and pyrotinib, were associated with broader TJP disruption compared with more selective agents. Despite the high incidence of TKI-associated diarrhoea, barrier-targeted therapeutic strategies were reported for only a limited number of agents.</p><p><strong>Conclusion: </strong>Overall, the available evidence suggests an association between TKI-induced diarrhoea and epithelial barrier disruption involving tight junction proteins, while also revealing important gaps in translational understanding and barrier-targeted therapeutic development.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080004","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":"Timosaponin AⅢ and Gefitinib Synergistically Inhibit NSCLC by Targeting RAGE/AKT/NF-κB/VEGF Pathway.","authors":"Mengfei Chen, Ting Xu, Huiting Peng, Hanshuang Cai, Yuchen Zhao, Xiying Li, Kaili Dong, Chuanfeng Liu, Jing Shi, Yuguo Liu","doi":"10.2174/0115680096488328260909072155","DOIUrl":"https://doi.org/10.2174/0115680096488328260909072155","url":null,"abstract":"<p><strong>Introduction: </strong>EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the standard therapy for EGFR-mutated advanced Non-Small Cell Lung Cancer (NSCLC). Gefitinib (GEF), as a first-generation EGFR-TKI, has made significant progress in the treatment of advanced lung cancer. However, acquired resistance leading to treatment failure severely limits its clinical benefits. Therefore, there is an urgent need for a new and effective strategy to improve the therapeutic effect of GEF.</p><p><strong>Methods: </strong>In this study, Timosaponin AⅢ (Tim-AⅢ) was combined with GEF for administration. The in vitro and in vivo efficacy of the combination in NSCLC cells was analyzed through cell viability assays, cell clone experiments, cell migration and invasion assays, flow cytometry, and animal experiments. The mechanism of the combination was analyzed and verified through RNA-seq and Western blotting experiments.</p><p><strong>Results: </strong>In this study, Tim-AⅢ and GEF showed a synergistic effect (CI<1). Compared with the single-drug groups, the combination group could inhibit cell proliferation, migration, and invasion, induce apoptosis, and arrest cells in the G0/G1 phase. The combination also significantly inhibited the growth of lung cancer cell xenografts in vivo without obvious toxicity. Mechanistically, this regimen could increase E-cadherin and downregulate Vimentin, thereby inhibiting the Epithelial-Mesenchymal Transition (EMT) process. It also downregulated the RAGE-mediated AKT/NF-κB/VEGF signaling pathway, thereby inhibiting tumor angiogenesis.</p><p><strong>Discussion: </strong>Tim-AⅢ combined with GEF exerts synergistic anti-tumor effects on NSCLC by regulating EMT and angiogenesis, with good biosafety. This combination provides a promising strategy to enhance the efficacy of EGFR-TKIs and supports further clinical translation.</p><p><strong>Conclusion: </strong>This study not only provides sufficient preclinical in vitro and in vivo pharmacological evidence for the synergistic anti-tumor effect of Tim-AⅢ and GEF, but also clarifies its new mechanism of action through two pathways-EMT and angiogenesis. This provides theoretical support for the development of new combined drug regimens in clinical practice.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036837","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":"MicroRNA-23C Impacts Hepatocellular Carcinoma Metastasis by Targeting OTUB1.","authors":"Ya-Nan Ji, Kai Wang, Zhong-Quan Yi, Si-Yu Gu, Wen-Chun Song, Hui Zhang, Ming Liu, Qing-Gan Ni, Xia Li","doi":"10.2174/0115680096457176260827075822","DOIUrl":"https://doi.org/10.2174/0115680096457176260827075822","url":null,"abstract":"<p><strong>Background: </strong>MicroRNA-23C (miR-23C) and Ovarian Tumor domain-containing Ubiquitin Aldehyde-Binding protein 1 (OTUB1) have been crucially implicated in numerous malignancies, such as Hepatocellular Carcinoma (HCC), a common malignant tumor. Herein, the function of the miR-23C-OTUB1-PI3K/AKT signaling pathway in HCC cell aggressiveness and Epithelial-Mesenchymal Transition (EMT) was explored, potentially revealing novel therapeutic approaches or targets for HCC.</p><p><strong>Methods: </strong>miR-23C expression was predicted and confirmed using bioinformatics analysis and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), respectively. The findings suggest miR-23C suppression was evaluated via the Cell Counting Kit 8 (CCK8), Transwell invasion, and wound healing assays. Western Blotting (WB) was employed to analyze EMT-related protein expression and the phosphorylation level of AKT (AK strain transforming). Target genes and binding sites were predicted using bioinformatics analysis, and their validation was confirmed by a dual-luciferase assay. The in vivo regulatory impact of miR-23C on target genes was confirmed using a model of nude mouse xenograft.</p><p><strong>Results: </strong>Both HCC tissues and cells exhibited miR-23C downregulation. While OTUB1 overexpression promoted HCC cell invasion, migration, and EMT, its knockdown, along with miR-23C upregulation, exerted a contrary effect. We further identified OTUB1 as a target gene of miR-23C, and in vivo experiments confirmed that miR-23C negatively regulated OTUB1 expression. Additionally, OTUB1 overexpression increased AKT phosphorylation, a phenomenon that was inhibited by OTUB1 silencing or transfection with the miR-23C mimic. Moreover, co-overexpression of OTUB1 and the miR-23C mimic counteracted the OTUB1 effects.</p><p><strong>Discussion: </strong>Our findings show miR-23C may suppress Hepatocellular Carcinoma (HCC) metastasis in experimental models by directly targeting OTUB1, potentially contributing to the inactivation of the PI3K/AKT pathway. These preliminary findings suggest that the miR-23C/OTUB1/AKT axis may warrant further investigation as a potential therapeutic target.</p><p><strong>Conclusion: </strong>Overall, in our preclinical models, miR-23C appeared to inhibit HCC cell aggressiveness and EMT by targeting OTUB1 and potentially regulating the PI3K/AKT pathway.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966941","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}