Current cancer drug targets最新文献

{"title":"Splicing: A New Dimension in Decoding the Complex Traits for Cervical Cancer.","authors":"Varsha Sai B, Ashwini Prabhu, Ratnacaram Chandrahas Koumar","doi":"10.2174/0115680096409242251125093718","DOIUrl":"https://doi.org/10.2174/0115680096409242251125093718","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer continues to pose a significant global health chal-lenge, with relatively high incidence and mortality rates among gynecological malignancies, particularly in developing countries. Complex etiological factors, including genetic predispo-sition, environmental influences, and biological mechanisms, regulate the progression of cer-vical cancer. Recent advances in understanding RNA splicing have contributed to a more de-tailed elucidation of these complexities, presenting a promising avenue for cervical cancer research. Here, we elucidate how alternative splicing events promote the synthesis of diverse protein isoforms that modulate tumorigenesis, progression, and metastasis.</p><p><strong>Methods: </strong>A PubMed and Google Scholar-based literature search was performed to identify genes involved in splicing mechanisms as biomarkers for cervical cancer. The search covered studies published between 2000 and 2024. The following keywords were used: \"splicing,\" \"splicing factors/genes,\" \"gene regulation,\" \"spliceosomes,\" \"splicing as cancer hallmark,\" and \"splicing mechanisms,\" in combination with \"cervical cancer.\" We included only English-language publications related specifically to splicing in cervical cancer.</p><p><strong>Results: </strong>We consolidated major splicing factors identified across genomic studies, clinical research, and mechanistic evaluations related to cervical cancer, which may serve as signifi-cant prognostic and diagnostic biomarkers.</p><p><strong>Conclusion: </strong>These consolidated findings highlight the potential impact of splicing on clinical decision-making, various therapeutic modalities, and personalized medicine. Furthermore, therapeutic strategies targeting splicing mechanisms could lead to novel interventions that im-prove clinical outcomes in cervical cancer patients.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834901","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 Regulation of Ferroptosis by circRNAs in Various Cancers.","authors":"Liushan Wei, Jia Yu, Shijie Wu, Guiqin Li, Yina Gong, Jiao Zeng, Xiaoyong Lei, Xiaoyan Yang","doi":"10.2174/0115680096453459260313072912","DOIUrl":"https://doi.org/10.2174/0115680096453459260313072912","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent and lipid-peroxidation-driven form of regulated cell death, has emerged as a central hub linking tumour initiation, metastatic spread, and resistance to radiotherapy and chemotherapy. At its core, labile Fe²⁺, which is imported via the transferrin/transferrin receptor axis, fuels Fenton chemistry by generating hydroxyl rad-icals that oxidise polyunsaturated fatty acids in membrane phospholipids. Cellular survival is heavily dependent on the system Xc⁻ antiporter, which imports cystine for glutathione (GSH) synthesis and thereby sustains glutathione peroxidase 4 (GPX4)-mediated detoxifi-cation of lipid peroxides. The collapse of this process precipitates ferroptosis, a form of reg-ulated cell death. Circular RNAs (circRNAs), defined as covalently closed, highly stable transcripts, have recently been identified as post-transcriptional regulators of this lethal cas-cade. By acting as effective 'sponges' for microRNAs, they effectively de-repress critical nodes of iron homeostasis, lipid remodelling, and ROS clearance. Select circRNAs have been observed to physically interact with GPX4 or Beclin-1, thereby either restraining or amplifying ferroptotic signalling. Consequently, circRNAs reprogramme the ferroptosis landscape of cancer cells, influencing proliferation, invasion, and therapy response. In this study, we synthesise and critically evaluate the current evidence for circRNA-mediated con-trol of ferroptosis across human malignancies. We also outline how circRNA silencing, over-expression, or genome editing could be exploited to synchronise iron depletion with conven-tional cytotoxic drugs. This offers a rational avenue to overcome chemo- and radio-re-sistance.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722042","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":"RUVBL1 Influences Immune Infiltration and Prognosis of Patients with Colon Adenocarcinoma.","authors":"Dabin Wu, Huiling Liu, Xuesong Xu, Hang Liu","doi":"10.2174/0115680096397636251129115450","DOIUrl":"https://doi.org/10.2174/0115680096397636251129115450","url":null,"abstract":"<p><strong>Introduction: </strong>RuvB-like protein 1 (RUVBL1) has been reported to be associated with tumor progression in various cancers. However, its role in colon adenocarcinoma (COAD) remains poorly understood.</p><p><strong>Methods: </strong>RUVBL1 mRNA and protein expression in COAD were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and UALCAN databases, respectively. The prognostic value of RUVBL1 was assessed based on The Cancer Genome Atlas (TCGA)-COAD datasets. Quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot assays were performed to confirm RUVBL1 expression levels in COAD and normal colon samples. RUVBL1-related genes in the TCGA-COAD datasets were identified using Spearman's correlation analysis, and RUVBL1-related immunomodulators were identified through the Tumor and Immune System Interaction Database (TISIDB). These genes and immunomodulators were subjected to functional enrichment analysis. Immune infiltration analysis was conducted to explore the association between RUVBL1 expression and tumor-infiltrating immune cells in COAD. The methylation status of RUVBL1 and its prognostic significance were analyzed using the MethSurv database.</p><p><strong>Results: </strong>Analysis of the GEPIA2 and UALCAN databases revealed that RUVBL1 expression was upregulated in COAD. Prognostic analysis indicated that RUVBL1 is a risk factor for poor survival in COAD patients. In vitro and in vivo experiments confirmed that RUVBL1 expression was higher in COAD samples compared to normal colon tissues. Functional enrichment analysis showed that RUVBL1-related genes and immunomodulators were primarily involved in immune and methylation-related processes. Immune infiltration analysis demonstrated that RUVBL1 expression was associated with 17 tumor-infiltrating immune cell types and negatively correlated with immune-related scores in COAD. Methylation analysis using the MethSurv database identified two RUVBL1 CpG sites that significantly influence the prognosis of COAD patients.</p><p><strong>Conclusion: </strong>These findings suggest that increased RUVBL1 expression is associated with poor prognosis and altered immune infiltration in COAD patients. RUVBL1 may serve as a potential therapeutic target for COAD.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721980","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":"EGFR and ALK Targeted Therapy Response in Non-Small Cell Lung Cancer Harboring Rare or Resistant Mutations: A Case Report and Molecular Insights.","authors":"Anju Farsana Abdul Gafoor, Preena S Parvathy, C Gopi Mohan, Keechilat Pavithran","doi":"10.2174/0115680096458810260330094454","DOIUrl":"https://doi.org/10.2174/0115680096458810260330094454","url":null,"abstract":"<p><strong>Introduction: </strong>The Non-Small Cell Lung Cancer (NSCLC) with rare genomic alterations poses a significant clinical challenge due to a lack of established therapeutic guidelines.</p><p><strong>Case presentation: </strong>We report the application of a precision medicine strategy integrating genomic profiling with in silico molecular docking to guide therapy for two patients harboring such rare mutations. Genomic analysis identified a rare EGFR exon 18/20 insertion in one patient and a resistant ALK C1156Y mutation in another. Selection of the appropriate drug was carried out using molecular docking simulations, which predicted high binding affinity of the irreversible EGFR inhibitor afatinib for the unique EGFR insertion and of the ALK inhibitor alectinib for the C1156Y-mutated kinase. We observed that the computationally-informed choices of afatinib and alectinib subsequently led to notable clinical and radiological improvements in the respective patients.</p><p><strong>Conclusion: </strong>The association between the docking predictions and clinical outcomes corroborates the utility of computational modeling for tailoring therapies, although the structural models provide mechanistic insight into drug efficacy against these rare mutations. The present integrated approach emphasizes the value of merging in silico methods into clinical decision-making to overcome the therapeutic uncertainty of uncommon oncogenic driver alterations.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722057","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":"Cisplatin Kills Ovarian Cancer Cells by Causing Mitochondrial Oxidative Stress and Death Through the TRPV1 Channel Stimulation: The Role of Eicosapentaenoic Acid.","authors":"Mevlüt Bucak, Mustafa Nazıroğlu","doi":"10.2174/0115680096401368251124072507","DOIUrl":"https://doi.org/10.2174/0115680096401368251124072507","url":null,"abstract":"<p><strong>Introduction: </strong>Cisplatin (Cisp) causes excessive Ca2+ and Zn2+ influxes mediated by TRPV1 channel stimulation and produces a high concentration of mitochondrial (mROS) and cytosolic (cROS) free reactive oxygen radicals. In clinical trials, it can be used in combination with other adjuvant medicinal agents to enhance the safety and efficacy of Cisp. Although contradictory findings exist, eicosapentaenoic acid (EPA) as an adjuvant has been shown to suppress the proliferation of ovarian cancer cells. We assessed the effects of EPA and Cisp incubations on oxidant levels, Zn2+, lysosomal injury, and apoptotic markers in the OVCAR-3 ovarian cancer cell line by activating TRPV1.</p><p><strong>Methods: </strong>Five groups were induced in the cells: control, Cisp (25 μM for 24h), EPA (100 μM for 24h), Cisp + EPA, and Cisp + TRPV1 antagonist (100 M capsazepine, CPZ).</p><p><strong>Results: </strong>Compared with control cells, Cisp mediated upregulation of Ca2+ entry and TRPV1 current density via TRPV1 stimulation in the cells. Cisp-mediated TRPV1 activation includes increases in mROS and cROS, mitochondrial dysfunction, and decreases in glutathione, glutathione peroxidase, OVCAR-3 viability, and number. In response to capsaicin, Cisp-mediated TRPV1 stimulation causes mitochondrial Ca2+ and Zn2+ overload, followed by increases in caspase-3/-8/-9, lysosomal injury, and apoptosis; however, these effects were less pronounced in the Cisp + EPA and Cisp + CPZ groups.</p><p><strong>Discussion: </strong>The tumor cell death effect of Cisp was decreased due to the suppression of TRPV1 caused by the CPZ and EPA incubations. Cisp via TRPV1 activation may therefore be an additional therapeutic approach to increase the susceptibility of ovarian tumor cells to mROS-dependent cell death.</p><p><strong>Conclusion: </strong>We observed that Cisp kills OVCAR-3 cells by stimulating TRPV1; even when the channel is blocked, Cisp retains anti-cancer effects. Cisp and TRPV1 stimulators together may provide an alternative method of killing ovarian cancer cells.</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":"147764964","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 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}