Current cancer drug targets最新文献

{"title":"Favorable Response to Bevacizumab Plus Capecitabine in a HER2-negative Breast Cancer Patient with Recurrent Brain Metastases: A Case Report.","authors":"Zihao Zhu, Pengfei Zhao, Luxuan Wang, Chunhui Li, Lijian Zhang","doi":"10.2174/0115680096495957260730114049","DOIUrl":"https://doi.org/10.2174/0115680096495957260730114049","url":null,"abstract":"<p><strong>Background: </strong>Brain metastases represent a major contributor to poor prognosis in cancer patients, with breast cancer-associated brain metastases accounting for a considerable proportion of cases. Owing to the presence of the Blood-Brain Barrier (BBB), most therapeutic agents for breast cancer fail to achieve effective concentrations in brain metastatic lesions. Notably, treatment options are extremely limited for patients with Human Epidermal Growth Factor Receptor 2 (HER2)-negative, Hormone Receptor (HR)-positive breast cancer complicated by brain metastases.</p><p><strong>Case presentation: </strong>In this study, we report the clinical treatment course of a 41-year-old female patient with HER2-negative, HR-positive breast cancer brain metastases. The patient experienced intracranial lesion progression following surgery, radiotherapy, and prior chemotherapy, and was subsequently administered a combination regimen of capecitabine and bevacizumab. Clinical symptoms were relieved after one cycle of treatment, and the therapeutic response was assessed as Partial Remission (PR). Prospective follow-up is ongoing. Following the first cycle of the combination regimen (initiated in February 2025), the patient achieved a partial response. As of the data cutoff date of December 9, 2025, the patient had maintained a Progression-Free Survival (PFS) of 10 months from the start of combination therapy. During the entire treatment course, the patient experienced only one episode of grade 3 myelosuppression (white blood cell count: 1.99 × 109/L; neutrophil count: 1.11 × 109/L), which was well controlled with symptomatic treatment. Capecitabine is characterized by its excellent ability to penetrate the BBB and Blood-Tumor Barrier (BTB), while bevacizumab can potentiate the efficacy of chemotherapeutic drugs via its anti- angiogenic activity.</p><p><strong>Conclusion: </strong>The combination of these two agents provided an effective therapeutic option for patients with HER2-negative, HR-positive breast cancer brain metastases, and thus provides a valuable clinical reference for the management of this patient population.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808343","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":"Leukocyte Receptor Tyrosine Kinase is A Novel Therapeutic Target In B-Cell Acute Lymphoblastic Leukemia.","authors":"Yujia Tao, Cheng Xing, Pengyu Zhang, Siwei Chen, Xindi Li, Chang Zhou, Wanyun Zuo, Hongling Peng","doi":"10.2174/0115680096478860260729071501","DOIUrl":"https://doi.org/10.2174/0115680096478860260729071501","url":null,"abstract":"<p><strong>Introduction: </strong>B-cell acute lymphoblastic leukemia (B-ALL) is associated with a poor prognosis, highlighting the need for novel therapeutic targets. Leukocyte receptor tyrosine kinase (LTK) is aberrantly activated in solid tumors; however, its role in B-ALL remains unclear. This study aimed to investigate the expression, functional significance, and therapeutic potential of LTK in B-ALL.</p><p><strong>Methods: </strong>LTK expression and its prognostic value were analyzed using public databases. Validation was performed on peripheral blood mononuclear cells from 17 B-ALL patients and 8 healthy donors via qRT-PCR and Western blot. Functional studies involved LTK knockdown via shRNA in the Nalm-6 B-ALL cell line, assessing proliferation, colony formation, and cell cycle progression in vitro, and tumor growth and infiltration in NOG mouse xenografts. The effects of lorlatinib on cell viability, PI3K/AKT signaling, MAPK/ERK signaling, and synergy with prednisone were evaluated using CCK-8 assays, Western blot, and combination index analysis.</p><p><strong>Results: </strong>LTK mRNA and protein levels were significantly elevated in B-ALL patients. Analysis of TARGET databases revealed a significant association between high LTK expression and shorter overall survival. LTK knockdown suppressed Nalm-6 cell proliferation, colony formation, and G1/S phase progression in vitro, extended survival in xenograft models, and reduced leukemic infiltration in bone marrow, peripheral blood, spleen, and liver. Lorlatinib inhibited Nalm-6 cell viability, downregulated phospho-AKT and phospho-ERK, and demonstrated synergistic cytotoxicity with prednisone.</p><p><strong>Conclusion: </strong>LTK is overexpressed in B-ALL and drives disease pathogenesis. Targeting LTK with lorlatinib, alone or in combination with prednisone, represents a promising therapeutic strategy for B-ALL.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808352","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":"Gut Bacterium Morganella morganii-Secreted Proteins Promote Colorectal Tumor Progression through CD137 Upregulation via NF-κB Activation.","authors":"Yuping Niu, Ruihong Xiao, Hui Sun","doi":"10.2174/0115680096490808260728112624","DOIUrl":"https://doi.org/10.2174/0115680096490808260728112624","url":null,"abstract":"<p><strong>Background: </strong>The development and progression of Colorectal Cancer (CRC) are closely linked to gut microbiota dysbiosis. However, the pathogenic functions and mechanisms of specific microbiota-derived factors in CRC are not well defined. In this study, we focused on Morganella morganii (M. morganii), a commensal bacterium significantly enriched in the gut of CRC patients, to investigate its potential role in promoting CRC progression.</p><p><strong>Methods: </strong>We first compared the fecal abundance of M. morganii between patients with CRC and healthy controls in a clinical cohort. From its culture supernatant, a high-molecularweight secreted protein mixture, designated M-T3, was purified. In vitro, HCT116 human CRC cells were treated with M-T3 to assess its effects on proliferation, clonogenic potential, and migration. The role of the NF-κB pathway was examined using pharmacological inhibition. In vivo, an HCT116 xenograft mouse model was established, and M-T3 was administered intratumorally. Tumor growth was monitored, and excised tumors were analyzed for expression of CD137 and proliferative activity.</p><p><strong>Results: </strong>Analysis of a clinical cohort revealed a significant enrichment of M. morganii in fecal samples from CRC patients compared to healthy controls. Mechanistically, treatment with M-T3 activated the NF-κB signaling pathway and consequently was associated with upregulation of CD137 in vitro. M-T3 treatment significantly enhanced the proliferation, clonogenicity, and migration of HCT116 cells, which were effectively reversed by NF-κB pathway inhibition. In vivo, intratumoral delivery of M-T3 accelerated tumor growth in HCT116 xenografts, accompanied by elevated tumor expression of CD137 and an increase in the proliferation marker Ki-67.</p><p><strong>Discussion: </strong>This work demonstrates that M. morganii promotes CRC progression via its secreted protein mixture, M-T3, through NF-κB signaling, and is associated with CD137 upregulation in tumor cells. Contrary to the classical view of CD137 as an immune costimulator, its tumor cell-intrinsic expression is associated with malignant phenotypes rather than confirmed functional causality. These findings establish a \"bacterial secretome-tumor signaling axis\" as a novel mechanism in microbiota-driven carcinogenesis.</p><p><strong>Conclusion: </strong>Collectively, our work showed that M. morganii promotes colorectal cancer progression via the secreted protein mixture M-T3, which activates the NF-κB signaling pathway and is associated with upregulation of CD137. These findings suggest a potential bacterial secretome-tumor signaling link in CRC. Further studies are required to identify the upstream sensing mechanism of M-T3 and determine the functional contribution of CD137 to M-T3-induced malignant phenotypes.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808395","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":"Integrating Large-Scale Bulk and Single-Cell RNA Sequencing with Machine Learning: Unveiling the Cytokine Landscape of Glioblastoma and Constructing a Prognostic Feature Model.","authors":"Longxiao Zhang, Xinyang Yan, Yunfei Zhou, Zhongbo Yang, Liangchao Jiang, Yi Shen, Jiaxi Li, Jinning Song","doi":"10.2174/0115680096458777260720110043","DOIUrl":"https://doi.org/10.2174/0115680096458777260720110043","url":null,"abstract":"<p><strong>Introduction: </strong>Cytokines play an important role in modulating the tumor microenvironment (TME) in glioblastoma multiforme (GBM). However, little work has focused on developing a prognostic model for GBM using cytokine signatures.</p><p><strong>Methods: </strong>Herein, we combined several GBM datasets, such as GSE163120, TCGA-GBM, CGGA-693, CGGA-325, GSE16011, the Rembrandt dataset, and GTEx. We combined the characteristic genes of different cell types in GBM samples with cytokine-associated genes identified in our previous research to identify single-cell cytokine-related genes (scCRGs). The enrichment scores of scCRGs in each cell were computed, and cells were stratified into a high-expression group and a low-expression group based on the median enrichment score. Differentially expressed scCRGs in the high-expression group were identified using the \"limma\" R package. Then, 117 combinations of machine learning (ML) algorithms were used to construct the new cytokine-related signature (CRS) prediction model. Moreover, we used consensus clustering algorithms to perform novel clustering analyses on GBM and subsequently conducted comprehensive immune profiling, response-to-immune-therapy prediction, and drug-sensitivity evaluation. Finally, we validated the key molecules in the model using tissue microarrays.</p><p><strong>Results: </strong>We identified 17 scCRGs that are mostly highly expressed in microglia. The new CRS model we proposed demonstrated strong predictive performance across the three independent cohorts, outperforming existing GBM models. Based on the CRS model, we identified distinct subgroups of GBM patients who may respond favorably to immunotherapy. The key gene AEBP1 in the model is highly expressed in GBM tissues.</p><p><strong>Discussion: </strong>Here, we present, for the first time, a highly reproducible and patient-specific prognostic prediction model based on a cytokine-related gene signature, combining several ML techniques and a large set of bioinformatic features. Compared with other published models, the proposed model is more stable and produces better predictions. Based on the model, we could identify separate subgroups of GBM patients who might respond better to immunotherapy, providing actionable information for the development of precision medicine approaches to treating GBM.</p><p><strong>Conclusion: </strong>CRS has the potential to be an effective and promising strategy for improving clinical outcomes in patients with GBM.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705710","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":"Hirsutanonol Inhibits the Progression of Hepatocellular Carcinoma by Promoting the Expression of CNDP1.","authors":"Youwen Du, Xiao Wang, Yueyue Xiao, Zhengxi Yang, Jingyu Yi, Zihang Xie, Jinxuan Feng, Xingyun Hao, Jiajun Zhu, Haichuan Wang, Shuomin Wang, Linxin Pan","doi":"10.2174/0115680096480354260717101124","DOIUrl":"https://doi.org/10.2174/0115680096480354260717101124","url":null,"abstract":"<p><strong>Objective: </strong>Hepatocellular Carcinoma (HCC) is a malignant tumor originating from hepatocytes. Hirsutanonol is a secondary metabolite derived from the bark of Alnus japonica that has multiple biological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, its role and underlying mechanism in hepatocellular carcinoma remain unclear. This study aimed to explore the effects of Hirsutanonol on HCC cells and its related molecular mechanism.</p><p><strong>Methods: </strong>First, EdU staining, Annexin V-FITC staining, cell scratch assays, Transwell chamber assays, and other experiments were performed to determine the effects of different concentrations of hirsutanonol on the proliferation, apoptosis, migration, and invasion of Huh7 cells. Furthermore, a mouse subcutaneous xenograft model was established to verify the inhibitory effect of Hirsutanonol on the in vivo growth of Huh7 cells. Molecular docking, CETSA, and Western blotting were subsequently performed to explore the binding interaction between Hirsutanonol and CNDP1 as well as the regulatory effect of Hirsutanonol on CNDP1 expression. Finally, rescue experiments were performed to investigate the influence of CNDP1 silencing on the tumor-suppressive function of hirsu-tanonol.</p><p><strong>Results: </strong>Hirsutanonol effectively inhibited the malignant biological behaviors of Huh7 cells, including proliferation, migration, and invasion, while promoting Huh7 apoptosis. Moreover, it suppressed the in vivo growth of Huh7 cells in mice. Mechanistic studies further confirmed that hirsutanonol can bind to CNDP1 and upregulate its expression, thereby inhibiting activation of the PI3K/AKT/mTOR signaling pathway. Moreover, silencing CNDP1 expression significantly reversed the inhibitory effects of Hirsutanonol on the proliferation, migration, and invasion of Huh7 cells, as well as its pro-apoptotic effect on Huh7 cells.</p><p><strong>Discussion: </strong>Hirsutanonol can effectively inhibit the proliferation, migration, and invasion of Huh7 cells, as well as their tumorigenicity in the subcutaneous layer of mice. Targeted binding to CNDP1 and promoting its expression may be important mechanisms through which Hirsutanonol exerts its anticancer function.</p><p><strong>Conclusion: </strong>Hirsutanonol can upregulate CNDP1 expression in a targeted manner and exhibit anticancer effects in HCC. These findings not only expand the biological functions of Hirsutanonol but also provide a theoretical basis for the pharmacological treatment of HCC in the future, thereby indicating that Hirsutanonol has a certain scientific significance and potential clinical application value.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599952","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":"Advances in Pharmacological Therapy for Recurrent High-Grade Meningiomas.","authors":"Ruining Bai, Shuo Yin, Yali Wang, Yiwen Zhang, Wenbin Li, Feng Chen","doi":"10.2174/0115680096470037260713093535","DOIUrl":"https://doi.org/10.2174/0115680096470037260713093535","url":null,"abstract":"<p><strong>Introduction: </strong>World Health Organization (WHO) grade 2 and 3 meningiomas are aggressive neoplasms characterized by high postoperative recurrence rates and unfavorable prognoses. Despite advances in surgical and radiotherapeutic management, effective systemic treatment options for recurrent WHO grade 2/3 meningiomas remain limited, with most therapies still under clinical investigation.</p><p><strong>Objective: </strong>To evaluate the efficacy and safety of various pharmacological treatment strategies for recurrent high-grade meningioma, including conventional chemotherapy, targeted therapy, and immunotherapy.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and ClinicalTrials.gov from database inception to August 2025. Relevant studies investigating conventional chemotherapy, targeted therapy, and immunotherapy for recurrent high-grade meningioma were systematically reviewed to summarize current advances in precision therapeutic strategies.</p><p><strong>Discussion: </strong>Conventional cytotoxic chemotherapy has demonstrated limited survival benefit in recurrent high-grade meningioma and is primarily used for palliative symptom management. In contrast, molecular targeted therapies have shown varying degrees of anti-tumor activity, including anti-angiogenic agents, Tyrosine Kinase Inhibitors (TKI), Focal Adhesion Kinase (FAK) inhibitors, and Mammalian Target of Rapamycin (mTOR) inhibitors. Among these, Bevacizumab demonstrated relatively favorable efficacy, prolonging median progression-free survival to 12-18 months in phase II clinical studies. Immunotherapy has also emerged as a promising therapeutic approach. Programmed death-1 (PD-1) inhibitors achieved 6-month progression-free survival rates (PFS-6) of up to 48% in early clinical studies. Furthermore, emerging immunotherapeutic strategies, such as chimeric antigen receptor T-cell (CAR-T) therapy, oncolytic virus (OVs) therapy, and personalized tumor vaccines, have demonstrated preliminary therapeutic potential. Nevertheless, developing standardized treatment strategies remains challenging due to limited clinical trial sample sizes, methodological heterogeneity, and substantial intertumoral and intratumoral molecular variability.</p><p><strong>Conclusion: </strong>Future research should prioritize molecular subtype-based therapeutic strategies to facilitate personalized treatment according to tumor biology. In addition, combination regimens integrating targeted therapy and immunotherapy may further improve therapeutic response and quality of life in patients with recurrent high-grade meningioma.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599925","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":"Targeting Oncogenic HER2 Mutations by Neratinib-induced HER2 Ubiquitination and Degradation in Breast Cancer.","authors":"Yingqiu Zhang, Xuesong Meng, Yueshun Hong, Xin Su, Yue Zhu, Jiayu Li, Jie Hu, Shaoxuan Cheng, Dian Yang, Shuyan Liu, Jinrui Zhang, Han Liu","doi":"10.2174/0115680096483929260709052728","DOIUrl":"https://doi.org/10.2174/0115680096483929260709052728","url":null,"abstract":"<p><strong>Background: </strong>Recent advances have revealed oncogenic HER2 mutations as an alternative tumorigenic mechanism independent of HER2 overexpression. Certain HER2 mutations confer resistance to current HER2-targeted therapies.</p><p><strong>Objective: </strong>Based on our previous finding that neratinib promotes HER2 endocytic degradation, its inhibitory effects were examined on drug-resistant oncogenic HER2 mutations.</p><p><strong>Methods: </strong>The intracellular distribution of HER2 was observed by immunofluorescence. The expression levels of HER2, pAKT, and pMEK with or without neratinib treatment were investigated by Western blotting. Proliferation was assessed using MTT, colony formation, and wound-healing assays. The tumorigenic potential of HER2 mutations was assessed in vivo. The effects of neratinib on HER2 mutants were investigated by colony and spheroid formation assays, and HER2 ubiquitination and intracellular localization were examined by immunoprecipitation and immunofluorescence, respectively.</p><p><strong>Results: </strong>HER2 mutations enhanced downstream AKT/MEK signaling and promoted tumor-igenesis in vitro and in vivo. Neratinib effectively suppressed downstream signaling, growth, and spheroid formation in cells expressing oncogenic HER2 mutants, including T733I, L755S, and the exon 16 deletion, which was accompanied by evidently enhanced ubiquitination and internalization of these mutants.</p><p><strong>Discussion: </strong>Neratinib effectively induces the ubiquitination and degradation of HER2 mutants to suppress oncogenic signaling. This feature provides a mechanistic explanation of neratinib activities against therapy-resistant HER2 mutations.</p><p><strong>Conclusion: </strong>Drug-resistant HER2 mutations can be suppressed by neratinib-induced endocytic degradation, resulting in effective suppression of cancer cell growth.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600071","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":"Targeting Ferroptosis in Adenocarcinoma of the Esophagogastric Junction: From a Natural Compound to Clinical Translation.","authors":"Xu-Dong Song, Jing-Jing Dai, Xiao-Guang Xu, Wen-Jun Mao","doi":"10.2174/0115680096484750260721112528","DOIUrl":"https://doi.org/10.2174/0115680096484750260721112528","url":null,"abstract":"<p><p>Ferroptosis-cell death driven by iron-is gaining traction in oncology. A study published in Current Cancer Drug Targets (CCDT) shows that a natural compound, Macranthoside B (MB), inhibits the activity of Adenocarcinoma of the Esophagogastric Junction (AEG) and that NRF2-mediated ferroptosis is involved in its regulation. This editorial discusses the mechanistic implications of that study, with particular attention to the NRF2/NCOA4-related ferritinophagy axis, while also emphasizing the limitations that should be addressed before clinical translation. Although the findings provide a useful preclinical rationale for exploring ferroptosis-oriented therapeutic strategies in AEG, key questions remain regarding the validation of the causal pathway, pharmacokinetics, systemic toxicity, tumor selectivity, model representativeness, and biomarker-based patient stratification. Therefore, Macranthoside B should currently be viewed as a promising experimental compound rather than a clinically established therapeutic candidate. Further in vivo studies and carefully designed translational investigations are required to determine whether this natural compound can be advanced toward AEG treatment.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600007","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":"LncRNA ABCA9-AS1 as a ceRNA Promotes Gastric Cancer Progression by Sponging miR-497-5p to Regulate KIF23 Expression.","authors":"Yiwen Wu, Yiniu Xia, Hanyu Liu, Shilin Wen, Keming Zhong, Qianwen Xiao, Zhou Wang, Xiaoyan Yang, Zhizhong Xie","doi":"10.2174/0115680096455467260703054748","DOIUrl":"https://doi.org/10.2174/0115680096455467260703054748","url":null,"abstract":"<p><strong>Introduction: </strong>Long noncoding RNAs (lncRNAs) have emerged as important modulators in the molecular pathology of cancer. lncRNA ABCA9-AS1 is a newly identified lncRNA, and its role in gastric cancer has not yet been reported.</p><p><strong>Objective: </strong>To investigate the effects of lncRNA ABCA9-AS1 on the proliferation and metastasis of gastric cancer cells and to explore its role in the miR-497-5p/KIF23 signalling cascade.</p><p><strong>Methods: </strong>A gastric cancer-specific ceRNA network (lncRNA-miRNA-mRNA) was constructed using RNA-seq and miRNA-seq data from TCGA. qRT-PCR was used to detect the expression levels of the target genes in gastric cancer cells (AGS, HGC-27, MKN28) and human gastric mucosal epithelial cells (GES-1). Knockdown of lncRNA ABCA9-AS1 was achieved using specific siRNA, while overexpression of KIF23 was achieved using a pcDNA3.1-based overexpression plasmid. The proliferative capacity of gastric cancer cells was assessed using CCK-8 and colony formation assays. Cell migration and invasion were evaluated by Transwell migration and Matrigel invasion assays, respectively.</p><p><strong>Results: </strong>A gastric cancer-specific lncRNA-associated ceRNA network was constructed. qRT-PCR showed significant upregulation of lncRNA ABCA9-AS1 in gastric cancer cells (AGS, HGC-27, MKN28), with concomitant downregulation of miR-497-5p and upregulation of KIF23. In AGS cells, ABCA9-AS1 knockdown increased miR-497-5p expression and reduced KIF23 expression, while miR-497-5p mimics suppressed KIF23 expression. Functional assays confirmed that ABCA9-AS1 knockdown and miR-497-5p overexpression inhibited the proliferation, migration, and invasion of AGS cells. Conversely, KIF23 restoration or miR-497-5p inhibition reversed these effects, as did KIF23 co-expression with miR-497-5p mimics.</p><p><strong>Discussion: </strong>Our results highlight lncRNA ABCA9-AS1 as a novel and promising prognostic biomarker that promotes gastric cancer progression by acting as a ceRNA to modulate the miR-497-5p/KIF23 axis.</p><p><strong>Conclusion: </strong>lncRNA ABCA9-AS1 is aberrantly upregulated in gastric cancer. As a ceRNA, it sponges miR-497-5p to increase KIF23 expression and enhance the proliferation, migration, and invasion of gastric cancer cells.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599962","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":"Overcoming Drug Resistance in Breast Cancer: Advances in Targeted and Combination Therapies.","authors":"Sandip Mondal, Manish Kumar Gautam, Tapan Kumar Mukherjee","doi":"10.2174/0115680096462629260713102634","DOIUrl":"https://doi.org/10.2174/0115680096462629260713102634","url":null,"abstract":"<p><p>In 2022, the Global Cancer Observatory (GLOBOCAN) predicted that female Breast Cancers (BCs) are the second most diagnosed cancer worldwide, accounting for 11.6% of all new cancer cases and estimated to account for 6.9% of all cancer deaths glob-ally. BC treatment options depend on factors such as tumor grade, stage, molecular subtype, and personalized considerations, including age, menopausal status, overall health, safety, and treatment efficacy. The traditional assessment of BC prognosis and treatment involves evaluating hormone receptor status (HRs: ER, PR, AR), human epidermal growth factor receptor 1 and 2 (HER1/EGFR, HER2), immune checkpoint markers (e.g., PD-L1), and cell signalling molecules (e.g., CDK4/6, PARP), among others. While TNBCs (ER-, PR-, HER2-) are mainly treated with chemotherapy, targeted therapy, and immunotherapy, either alone or in combination, HRs and/or HER2 remain the primary therapeutic targets for ER/PR+HER2+ and ER/PR+HER2- BCs, respectively. However, challenges such as de novo and acquired resistance, toxicity, and side effects limit the effectiveness of targeted therapies. This review discusses the advancement of conventional targeted therapies against BCs by introducing new generations of targeted molecules, including advanced SERMs, SERDs, AIs, CDK4/6, and PARP inhibitors, various ADCs, PROTACs, CERANs, and SERCAs.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599950","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}