Current cancer drug targets最新文献

{"title":"Integrated Computational and Experimental Discovery of a Promising Xanthine Derivative with Anticancer Potential Targeting EGFR.","authors":"Eslam B Elkaeed, Reda G Yousef, Hazem Elkady, Hanan A Al-Ghulikah, Ibrahim M Ibrahim, Omar A Soliman, Dalal Z Husein, Ahmed S Doghish, Ahmed M Metwaly, Ibrahim H Eissa","doi":"10.2174/0115680096363027250731042338","DOIUrl":"https://doi.org/10.2174/0115680096363027250731042338","url":null,"abstract":"<p><strong>Introduction: </strong>Epidermal Growth Factor Receptor (EGFR) is a well-established therapeutic target in cancer treatment. In this study, a novel N-phenylacetamide derivative of theobromine, designated as T-1-PA, was designed as a potential semisynthetic EGFR inhibitor.</p><p><strong>Method: </strong>The 3D structure, stability, and electronic reactivity of T-1-PA were determined using Density Functional Theory (DFT) analyses. Molecular docking, molecular dynamics (MD) simulations, Molecular Mechanics Generalized Born Surface Area (MM-GBSA), Protein-Ligand Interaction Profiler (PLIP), and Principal Component Analysis of Trajectories (PCAT) were employed to evaluate the binding affinity and inhibitory potential of T-1-PA against EGFR. Computational ADMET profiling was conducted to predict drug-likeness and safety. Subsequently, T-1-PA was semisynthesized and subjected to in vitro biological evaluation.</p><p><strong>Results: </strong>Computational analyses demonstrated a strong binding affinity of T-1-PA to EGFR. The compound exhibited favorable ADMET properties. In vitro assays revealed potent EGFR inhibition with an IC₅₀ of 0.736 ± 0.005 μM. T-1-PA also inhibited the proliferation of HepG2 and MCF7 cancer cell lines with IC₅₀ values of 0.88 ± 0.01 μM and 1.13 ± 0.01 μM, respectively. Flow cytometry analysis indicated induction of apoptosis and G1 phase cell cycle arrest in HepG2 cells. Additionally, T-1-PA significantly impaired HepG2 cell migration and wound-healing capacity.</p><p><strong>Discussion: </strong>The results validate the computational predictions and highlight the anticancer potential of T-1-PA through EGFR inhibition and antiproliferative activity. The compound's favorable pharmacokinetic and safety profiles further support its therapeutic promise.</p><p><strong>Conclusion: </strong>T-1-PA is a promising semisynthetic compound with selective antiproliferative activity mediated via EGFR inhibition. These findings encourage further preclinical investigation of T-1-PA as a novel candidate for EGFR-targeted cancer therapy.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205734","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":"Comprehensive Immune Subtyping and Multi-Omics Profiling of the Tumor Microenvironment in Colorectal Cancer: Implications for Prognosis and Personalized Immunotherapy.","authors":"Bailing Zhou, Zhiwei Li, Shengxian Fan, Hao Wang, Jihua Wang","doi":"10.2174/0115680096395386250910130110","DOIUrl":"https://doi.org/10.2174/0115680096395386250910130110","url":null,"abstract":"<p><strong>Introduction: </strong>The Tumor microenvironment (TME) plays a crucial role in colorectal cancer (CRC) prognosis and treatment response. However, comprehensive understandings of TME-related immune subtypes and their mechanisms for precision medicine remain insufficient. This study aims to identify immune subtypes in CRC, develop a prognostic model, and explore the role of microbial diversity in tumor progression.</p><p><strong>Methods: </strong>Multi-omics data and non-negative matrix factorization (NMF) were used to classify CRC into immune subtypes. Differentially expressed TME-related genes were identified, and a prognostic risk model was developed using Cox and LASSO regression. Single-cell RNA sequencing (scRNA-seq) assessed cellular interactions and gene set variations. Microbiome profiling was integrated to evaluate the impact of microbial diversity on CRC progression and immune modulation. Key findings were validated using immunohistochemistry, external datasets, and qPCR in patient-derived organoids.</p><p><strong>Results: </strong>Four TME-related immune subtypes were identified: immune-exhausted C1 (poor prognosis, high immune infiltration), immune-activated C2/C3 (better prognosis), and immune-desert C4 (worst prognosis). A risk model based on genes (SOX9, CLEC10A, RAB15, RAB6B, PCOLCE2, FUT1) stratified patients into high- and low-risk groups. High-risk groups exhibited increased Enterobacteriaceae and Clostridium, while low-risk groups showed higher Porphyromonadaceae and Peptostreptococcaceae, correlating with better immunotherapy responses. scRNA-seq revealed distinct cell-cell communication patterns across subtypes.</p><p><strong>Discussion: </strong>The study highlights the complexity of CRC's TME and its role in prognosis and treatment. Findings support personalized treatment strategies, considering immune and microbial factors.</p><p><strong>Conclusion: </strong>This research integrates TME subtyping, risk modeling, single-cell analysis, and microbiome profiling to advance CRC prognosis and precision therapy, emphasizing personalized strategies for better outcomes.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198606","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 Impact of Young Age on Breast Cancer Prognosis: A Systematic Review and Meta-Analysis.","authors":"Yongxin Li, Yuanfang Xin, Chengrong Zhang, Jingchuan Qi, Yuyao Tang, Zhoujuan Li, Miaozhou Wang, Zhen Liu, Dengfeng Ren, Zitao Li, Yongzhi Chen, Jinming Li, Hongxia Liang, Yan Zhang, Zhengbo Xu, Jiuda Zhao","doi":"10.2174/0115680096369006250909091053","DOIUrl":"https://doi.org/10.2174/0115680096369006250909091053","url":null,"abstract":"<p><strong>Introduction: </strong>There is no consensus on the impact of young age (≤ 35 or 40) on breast cancer prognosis. In this study, a meta-analysis was carried out on the prognosis of breast cancer in young women.</p><p><strong>Methods: </strong>We searched PubMed, Embase, Web of Science, Cochrane, and key cancer-related international conference proceedings, from their inception to 1st June, 2023, with an update on 15th July, 2023. Studies were included if they reported hazard ratios (HRs) with 95% confi-dence intervals (CIs) or presented Kaplan-Meier survival curves. The main outcomes were overall survival (OS), disease-free survival (DFS), breast cancer-specific survival (BCSS), lo-cal recurrence-free survival (LRFS), distant disease-free survival (DDFS), progression-free survival (PFS), and pathological complete response (pCR). This meta-analysis was registered in PROSPERO (CRD42023459282).</p><p><strong>Results: </strong>The meta-analysis, including 129 studies with approximately 1,065,000 patients, re-ported that young breast cancer (YBC) patients had worse OS (HR = 1.30; 95% CI: 1.17 - 1.43; I² = 93%; P < 0.01), DFS (HR = 1.58; 95% CI: 1.47 - 1.70; I² = 68%; P < 0.01), BCSS (HR = 1.28; 95% CI: 1·09 - 1.49; I² = 95%; P < 0.01), LRFS (HR = 2.05; 95% CI: 1.59 - 2.59; I² = 70%; P < 0.01), DDFS (HR = 1.44; 95% CI: 1.11 - 1.87; I² = 91%; P < 0.01), and PFS (HR = 1.54; 95% CI: 1.16 - 2·03; I² = 90%; P < 0.01) and a greater pCR rates than non-young breast cancer (NYBC) patients (odds ratio (OR) = 1.45; 95% CI: 1.16 - 1.82; I² = 87%; P < 0.01). Subgroup analysis demonstrated that, compared with NYBC patients, certain differences were found in the prognoses of YBC patients with different molecular subtypes, regions, and stages.</p><p><strong>Discussion: </strong>This meta-analysis confirmed that YBC patients have worse survival outcomes than NYBC patients, despite having higher pCR rates. Subgroup analyses demonstrated that outcomes varied by molecular subtype, region, and disease stage. These findings underscore the importance of early screening, enhanced patient education, and tailored treatment strategies for YBC patients.</p><p><strong>Conclusion: </strong>Patients with YBC had worse OS, DFS, BCSS, LRFS, DDFS, PFS, and greater pCR rates than NYBC patients.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198167","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":"Identification of the Immune Microenvironment, Mutation Burden, Immunotherapy, and Drug Sensitivity Related to Lung Adenocarcinoma Tumor Stem Cells via WGCNA.","authors":"Qi Liu, Liusheng Wu, Meiling Lu, Hao Jia, Xiaoqiang Li","doi":"10.2174/0115680096337566250906092330","DOIUrl":"https://doi.org/10.2174/0115680096337566250906092330","url":null,"abstract":"<p><strong>Objective: </strong>To analyze LUAD cases in The Cancer Genome Atlas (TCGA), the mRNA expression-based stemness index (mRNAsi) was used. Models of cancer immunity and LUAD prognosis were developed on the basis of correlations between immune and stem cell genes.</p><p><strong>Methods: </strong>We investigated the differential expression of mRNA dryness index (mRNAsi) in LUAD, survival prognosis, and correlation with clinical parameters. Iden-tify key mRNAsi-related modules and genes by weighted gene co-expression network analysis (WGCNA). Gene set enrichment analysis (GSEA/GSVA) was used to identify stem cell markers and immune-related differentially expressed genes (SC IRGs), and 10 key genes were enriched. Subgroup enrichment, gene mutations, genetic correlated-ness, gene expression, immunity, tumor mutational burden (TMB), and drug sensitivity were further performed in the comprehensive analysis of pivot genes and subgroups.</p><p><strong>Results: </strong>Compared with normal cells, LUAD cells presented significantly greater mRNAsi values through differential expression analysis. The mRNAsi was highly cor-related with clinical parameters (age, sex, and T stage). On the basis of WGCNA, blue-green and brown modules were identified as the most significant modules (including positive and negative correlations) associated with mRNAsi expression. The functions and pathways of the two mRNAsi-related modules were enriched mainly in tumor oc-currence, development, and metastasis. Cox regression analysis was used to identify 30 SCIRGs associated with prognosis by combining the stem cell indices of the DEGs and the immune-related DEGs. A LASSO regression model was constructed after 10 DEGs related to the prognosis of patients with LUAD were detected. There were significant differences between the high-risk and low-risk groups in terms of GSEA/GSVA, im-mune cell correlation, clinical correlation, etc., following model validation (P<0.05).</p><p><strong>Discussion: </strong>There are a total of 10 genes in our study model, including four key pre-dictors: DGRIK2, PTTG1, LGR4, and PDGFB. The other 6 genes need to be further delineated and verified. To date, our research has some limitations and has not been validated in cell or animal experiments. These findings provide a relevant theoretical basis for subsequent experimental research on lung adenocarcinoma stem cells. Further research into these cancer stem cell genes will increase the likelihood that they play a role in cancer. There is an opportunity to use it as a therapeutic target for targeted ther-apy for lung adenocarcinoma in the future.</p><p><strong>Conclusion: </strong>mRNAsi is associated with immunity, which was previously overlooked in the gene analysis of LUAD stem cells. These key genes have a strong overall corre-lation, which can be achieved by inhibiting the stemness characteristics of cancer cells, which may lay the foundation for future research on LUAD.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198622","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":"Unravelling the Mechanism of Methylophiopogonanone A Against Esophageal Squamous Cell Carcinoma Based on Network Pharmacology and Molecular Docking.","authors":"Chen-Tai Qin, Yu-Shui Ma, Siliang Wang, Jia Wu, Miao-Miao Zheng, Wen-Lian Chen","doi":"10.2174/0115680096387327250906212020","DOIUrl":"https://doi.org/10.2174/0115680096387327250906212020","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal squamous cell carcinoma (ESCC) stands as one of the deadliest cancers globally. Given the urgent clinical need for more precise and comprehen-sive therapeutic strategies, the phytocompound methylophiopogonanone A (MO-A) demon-strates the potential as a candidate for ESCC treatment. This study aimed to verify the ther-apeutic effect of MO-A against ESCC and unveil its underlying mechanism.</p><p><strong>Methods: </strong>Three compound-protein interaction databases were utilized to predict the molec-ular targets of MO-A. Subsequently, potential therapeutic targets of ESCC were identified based on the GEO database. KEGG pathway and GO function enrichment analyses were then performed by using these two sets of targets, respectively. Through the integrative anal-ysis of these two target sets, core targets of MO-A with therapeutic potential against ESCC were determined. Protein-protein interaction network analyses and molecular dockings were executed by using these targets. Two human-derived ESCC cell lines were enrolled for bio-logical validation, including cell viability, colony formation, and cell cycle assays.</p><p><strong>Results: </strong>This study predicted 200 potential targets of MO-A and uncovered 138 key targets associated with the progression of ESCC. Enrichment analyses and PPI networks under-scored the involvement of cell cycle-related genes in ESCC development. Four proteins were determined as core MO-A targets for ESCC treatment, including AURKA, AURKB, CDC25B, and TOP2A, which partake in the regulation of the cell cycle. Finally, the inhibi-tory effect of MO-A on ESCC cell proliferation was validated in vitro, primarily through inducing cell cycle arrest at the G2/M phase in ESCC cells.</p><p><strong>Discussion: </strong>These results revealed the anti-ESCC potential of MO-A, a plant-derived fla-vonoid, using integrated bioinformatics and biological experiments. While findings provide a mechanistic basis for the efficacy of MO-A, limitations include reliance on computational and in vitro models. Further studies should be conducted to evaluate the pharmacological properties and safety of MO-A across multiple models, alongside more comprehensive structure-activity relationship studies to inform drug optimization prior to clinical transla-tion.</p><p><strong>Conclusion: </strong>MO-A can impede ESCC growth by triggering cell cycle G2/M arrest, posi-tioning it as a novel and promising phytocompound for ESCC therapy.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184626","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":"Multi-omics Approaches to CCAAT/Enhancer-Binding Protein Beta in Oral Squamous Cell Carcinoma: Crosstalk Between Tumor Cells and Tumor-Associated Macrophages Driving Disease Progression.","authors":"Min Li, Jilun Liu, Wenjuan Zhang, Ruonan Sun, Wenjing Wang, Xin Liu, Linyu Jin, Yongle Qiu","doi":"10.2174/0115680096387374250823190214","DOIUrl":"https://doi.org/10.2174/0115680096387374250823190214","url":null,"abstract":"<p><strong>Background: </strong>CCAAT/Enhancer-Binding Protein Beta (CEBPB) is an important transcription factor that regulates tumor progression. However, the mechanism by which CE-BPB regulates the progression of Oral Squamous Cell Carcinoma (OSCC) remains incom-pletely understood. Tumor progression depends on complex intercellular interactions within the tumor microenvironment. The purpose of this study was to investigate the role and epige-netic regulatory mechanisms of CEBPB in interactions between OSCC cells and tumor-infil-trating immune cells.</p><p><strong>Methods: </strong>Bulk RNA-seq, ChIP-seq, and scRNA-seq data were obtained from The Cancer Ge-nome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. The HOMER algorithm was employed to identify enhancers and predict the CEBPB-binding mo-tif. Cell cluster analysis, functional enrichment, and intercellular interaction analysis were per-formed using the \"Seurat\" R package. H3K27ac enrichment at GAS6 enhancers was validated by ChIP-qPCR. Metastatic OSCC cells with CEBPB knockdown or GAS6 overexpression were established and co-cultured with THP-1 cells. IL-10 and IL-6 secretion from co-cultured THP-1 cells was detected via ELISA. Chemotaxis of OSCC cells toward THP-1 cells was assessed through a Transwell assay.</p><p><strong>Results: </strong>CEBPB was upregulated in OSCC and correlated with poor prognosis. By integrating H3K27ac ChIP-seq and bulk RNA-seq data, 131 CEBPB-regulated enhancer-controlled genes were identified in lymph node metastatic OSCC cells. scRNA-seq analysis revealed eight ma-jor cell clusters in primary foci and lymph node metastases, including T/NK cells, malignant epithelial cells, B/plasma cells, macrophages, fibroblasts, dendritic cells, endothelial cells, and mast cells, with the malignant epithelial cells stratified into distinct sub-clusters. CEBPB ex-pression was elevated in malignant epithelial cells of lymph node metastases compared to pri-mary foci. Furthermore, 15 pairs of enhanced ligand-receptor interactions were identified in lymph node metastases relative to primary foci. GAS6 was a CEBPB-regulated enhancer-con-trolled gene, primarily mediating interactions between malignant cells and macrophages. CE-BPB knockdown in metastatic OSCC cells significantly impaired their chemotaxis toward co-cultured THP-1 cells, and downregulated IL-10/IL-6 secretion and CD206 expression in co-cultured THP-1 cells. Conversely, GAS6 overexpression reversed these inhibitory effects.</p><p><strong>Conclusion: </strong>CEBPB activated GAS6 transcription in metastatic OSCC cells. The CE-BPB/GAS6 axis in metastatic OSCC cells enhanced their chemotaxis toward macrophages and promoted the M2 polarization of macrophages, thereby facilitating the establishment of an immunosuppressive microenvironment.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111985","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":"Grafting of Resveratrol-Chitosan Nanoparticles as a Promising Radiosensitizer and Protector in DMBA-Induced Breast Cancer in Mice.","authors":"Mohammed Abdalla Hussein, Ahmed M Hamdy, Ibrahim G Abdelrhman, Mohamed Auf, Eman R Saifeldeen, Sahar M Elashmony, Suzan S Abuelkasem, Azza M Metwaly","doi":"10.2174/0115680096364549250828062651","DOIUrl":"https://doi.org/10.2174/0115680096364549250828062651","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Breast cancer is the most common malignancy among women and the second leading cause of cancer-related deaths worldwide. Resveratrol, a polyphenolic stilbene derivative found in grapes, red wine, and other plants, possesses anti-cancer properties. Various studies have reported the potential of different nanomaterials to act as radiosensitizers against tumor cells. This study aimed to evaluate the antitumor and radiosensitizing effects of Resveratrol-Chitosan Nanoparticles (Res-Ch-NPs) in a DMBA-induced breast cancer mouse model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Res-Ch-NPs were developed using the chitosan emulsification cross-linking technique. The particle size, entrapment efficiency, zeta potential, UV and FT-IR spectra, and drug release profile of Res-Ch-NPs were evaluated. The IC50 of Res-Ch-NPs, both individually and in combination with γ-irradiation, was calculated against the MCF-7 cell line using the MTT assay. The LD50 of Res-Ch-NPs was estimated, and 1/20 LD50 was used to assess the antitumor and radiosensitizing effects on breast cancer cell-bearing mice. The in vivo efficacy was evaluated in DMBA-induced breast cancer mice, examining tumor weight, volume, blood parameters (Hb%, RBCs, and WBCs), oxidative stress markers (MDA, GSH, SOD, and CAT), immune markers (INF-γ, TGF-β1, CD4, and CD8), and gene expression levels (p53, survivin, and STAT3). Additionally, histopathological examination of breast tissues was also carried out.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Res-Ch-NPs demonstrated high entrapment efficiency (82.46 ± 1.02), a polydispersity index (0.65 ± 0.03), and a particle size of 184.60 ± 17.36 nm with a zeta potential of -46.78 ± 0.57 mV. The UV spectra of resveratrol and Res-Ch-NPs showed strong absorption at 230 and 250 nm. FTIR analysis confirmed the chemical stability of resveratrol in Res-Ch-NPs. The maximum release of Res-Ch-NPs was recorded at 55.07% after 44 hours. The IC50 values of Res-Ch-NPs, both individually and combined with γ-irradiation, against MCF-7 cell viability were 38.26 and 24.8 ± 0.76 μg/mL, respectively. The LD50 of Res-Ch-NPs was found to be 2090 mg/kg body weight. Treatment of DMBA-injected mice with Res-Ch-NPs and γ-irradiation significantly reduced tumor weight and volume, improved blood Hb%, RBC, and WBC levels, as well as breast MDA, GSH, SOD, and CAT levels. Additionally, breast levels of INF-γ, TGF-β1, CD4, and CD8 were reduced in DMBAinjected mice treated with Res-Ch-NPs and γ-irradiation. Conversely, the combination treatment upregulated p53 in breast cells and downregulated the expression of survivin and STAT3 genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The findings confirmed that Res-Ch-NPs enhanced radiosensitivity, facilitating tumor regression and immune restoration. The modulation of pro-inflammatory and antioxidant pathways suggests a dual therapeutic role, acting as both a radiation enhancer and a tumor-suppressing agent. However, further research is needed ","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014067","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":"Lipidomic Profiling in Cancer: Phospholipid Alterations and their Role in Tumor Progression.","authors":"Swarnima Paliwal, Swaroop Kumar Pandey","doi":"10.2174/0115680096398874250818210830","DOIUrl":"https://doi.org/10.2174/0115680096398874250818210830","url":null,"abstract":"<p><p>Phospholipids play a crucial role in various aspects of cancer biology, including tumor progression, metastasis, and cell survival. Recent studies have highlighted the signifi-cance of phospholipid metabolism and signaling in multiple cancer types, such as breast, cer-vical, prostate, bladder, colorectal, liver, lung, melanoma, mesothelioma, and oral cancer. Al-terations in phospholipid profiles, particularly in phosphatidylcholine and phosphatidylethan-olamine, have been identified as potential biomarkers for cancer diagnosis and prognosis. Moreover, specific phospholipids and their metabolic pathways have been implicated in cancer cell proliferation, migration, invasion, and resistance to therapy. Enzymes involved in phos-pholipid metabolism, such as phospholipases, choline kinase, and autotaxin, have emerged as promising therapeutic targets. The harmony between phospholipids and oncogenic signaling pathways, such as PI3K/AKT and Wnt/β-catenin, further emphasizes their importance in can-cer progression. Additionally, phospholipids have been shown to modify the tumor microen-vironment, influencing immune responses and angiogenesis. The application of advanced lip-idomic profiling techniques, such as mass spectrometry, has facilitated the identification of novel phospholipid biomarkers and provided insights into the metabolic reprogramming of cancer cells. Furthermore, phospholipid-based nanocarriers have demonstrated potential in tar-geted drug delivery and cancer immunotherapy. In conclusion, the multifaceted roles of phos-pholipids in cancer biology highlight their significance as diagnostic markers, prognostic in-dicators, as well as therapeutic targets, offering new avenues for cancer management and treat-ment. This review is conducted in order to answer three questions: What is the role of phos-pholipids in different types of cancer? What are the key lipidomic biomarkers for different cancers? What are the key effects of phospholipids on various types of cancer cell survival?</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014104","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":"Driver Genes and Genomic Instability Predict the Incidence and Outcome of Brain Metastases.","authors":"Hainan Yang, Weiping Hong, Jie Ding, Weifang Yuan, Hui Ye, Tao Lin, Qingjun Hu, Xin Jin, Lei Wen, Da Liu, Ming Lei","doi":"10.2174/0115680096385277250818184435","DOIUrl":"https://doi.org/10.2174/0115680096385277250818184435","url":null,"abstract":"<p><strong>Introduction: </strong>The incidence of brain metastases in patients diagnosed with ad-vanced lung cancer is high, drawing significant attention to the risk factors associated with this progression.</p><p><strong>Methods: </strong>A total of 252 advanced non-small cell lung cancer (NSCLC) patients with brain metastases were enrolled in this study between July 2018 and December 2023 from our hos-pital. Additionally, driver genes, including EGFR, ALK, ROS1, KRAS, and RET, were doc-umented. Next-generation targeted sequencing of a 168-gene panel was conducted on all col-lected samples to explore the association between tumor genomic complexity and risk factors for NSCLC with brain metastases.</p><p><strong>Results: </strong>Among 252 lung cancer patients with brain metastases enrolled in this research, the most prevalent driver gene was EGFR, accounting for 39.29% (99 patients). Other driver gene mutations, such as KRAS, ALK, ROS1, and RET, accounted for 3.57%, 7.14%, 2.78%, and 0.4%, respectively. Kaplan-Meier analysis showed that patients with EGFR mutations had a more favorable overall survival (OS) compared to those without the mutation (P < 0.0001). Additionally, patients with ALK fusions had longer survival times compared to those with wild-type genes (P = 0.0021). In this study, patients were divided into two groups based on the presence or absence of copy-number alterations. Further survival analysis revealed that patients with copy-number alterations experienced significantly shorter overall survival com-pared to the control group (P = 0.041).</p><p><strong>Discussion: </strong>This study underscores the crucial role of driver mutations and genomic instability in advanced NSCLC with brain metastases, where EGFR and ALK alterations are linked to better survival. In contrast, high genomic complexity is associated with worse outcomes.</p><p><strong>Conclusion: </strong>Driver gene mutations are present in more than half of the patients with central nervous system (CNS) failure. Genomic instability, characterized by the number of co-occur-ring mutated genes and copy-number alterations, is a risk factor associated with shorter sur-vival time.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014117","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":"High Glucose and Glucose-derived Intermediates are Linked To Lung Cancer Aggressiveness.","authors":"Himani Joshi, Raiyan Satti, M Saeed Sheikh","doi":"10.2174/0115680096415724250822061328","DOIUrl":"https://doi.org/10.2174/0115680096415724250822061328","url":null,"abstract":"","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999879","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}