Discover. Oncology最新文献

{"title":"Integrative multi-omics analysis identifies histone methyltransferase SUV420H2 as a prognostic biomarker in clear cell renal cell carcinoma.","authors":"Subhadip Kundu, Rupal Tripathi, Anurag Mehta, Amitabh Singh, Ashish Khanna, Sudhir Kumar Rawal","doi":"10.1007/s12672-026-05556-2","DOIUrl":"https://doi.org/10.1007/s12672-026-05556-2","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) remains a clinically challenging malignancy characterized by high heterogeneity, limited early biomarkers, and suboptimal response rates to current targeted and immune-based therapies. Increasing evidence highlights that dysregulated epigenetic mechanisms, particularly altered histone methylation, contribute to tumor progression, metabolic reprogramming, and immune escape in RCC. However, the specific regulatory networks linking epigenetic modifiers with transcriptomic rewiring and therapeutic vulnerabilities in clear cell RCC (ccRCC) remain poorly defined. In this multi-omics in silico study, we systematically screened all histone methyltransferases and identified SUV420H2 (also known as KMT5C) as the most consistently overexpressed gene associated with adverse clinical outcomes in ccRCC. SUV420H2 showed stepwise upregulation with tumor stage and grade, while promoter analysis revealed multiple significantly hypomethylated CpG sites, suggesting a potential epigenetic deregulation. Complementarily, six predicted SUV420H2-targeting miRNAs were significantly downregulated in ccRCC consistent with post-transcriptional regulatory control. SUV420H2 overexpression correlated with increased CD4⁺/CD8⁺ T-cell infiltration, indicating an association with altered immune infiltration patterns. Co-expression and enrichment analyses revealed strong associations with chromatin organization, mitotic regulation, RNA metabolic processes, and RNA splicing, from which a five-gene RNA-processing signature (KAT2A, SNRNP70, CCNL2, CLK2, AKAP17A) was derived. This signature was strongly correlated with SUV420H2 and was associated with poorer overall survival specifically in ccRCC. Drug-sensitivity profiling further showed that high SUV420H2/RNA-processing signature expression conferred increased sensitivity to FK866 (NAMPT inhibitor), topoisomerase inhibitors, and apoptosis-inducing agents, identifying potential therapeutic associations that warrant further investigation. Collectively, our findings suggest that SUV420H2 is a multi-layer dysregulated epigenetic regulator associated with ccRCC progression and highlight its RNA-processing network as a promising prognostic and therapeutic axis.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444396","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":"Development of high-grade glioma as a second malignant neoplasm in patients treated for primary brain tumors.","authors":"Cheng Li, Chuan Zhao, Jingjing Ge, Chi Zhao, Shaopei Qi, Fengjun Xue, Jingjing Zhang, Junping Zhang","doi":"10.1007/s12672-026-05090-1","DOIUrl":"10.1007/s12672-026-05090-1","url":null,"abstract":"<p><strong>Purpose: </strong>Second malignant neoplasms (SMNs) represent a devastating late complication of central nervous system (CNS) tumor, particularly in pediatric and young adult populations. While improved treatments have increased survival rates, the risk and characteristics of SMNs in contemporary cohorts remain poorly characterized. The purpose of this study is to characterize the clinicopathological and molecular features of therapy-related high-grade gliomas(t-HGGs), and to explore their multifactorial etiology involving radiation, chemotherapy, and potential genetic susceptibility.</p><p><strong>Methods: </strong>We analyzed seven cases of histologically confirmed SMNs developing after treatment for primary CNS tumors. We collected and analyzed key clinical information from patients, including gender, age, time to second tumor onset (latency), treatment modalities, and outcomes. Additionally, we examined imaging findings, histopathological features using hematoxylin-eosin (H&E) staining and immunohistochemistry, as well as molecular marker characteristics.</p><p><strong>Results: </strong>The cohort consisted of seven patients (5 males, 2 females). The median age at primary tumor diagnosis was 5 years (range: 3-21 years), and at SMN diagnosis was 12 years (range: 7-27 years), with a median latency of 6 years (range: 2-9 years). All patients received radiotherapy. Exploratory analysis revealed no significant relationship between radiation dose and latency period. Histological transformation was universal, most commonly from medulloblastoma to high-grade glioma (3/7 cases) and germ cell tumors (3/7 cases, including 2 germinomas and 1 non-germinomatous germ cell tumor (NGGCT)). Molecular analysis in sequenced cases revealed distinct profiles, including NF1/PDGFRA alterations. Outcomes were poor.</p><p><strong>Conclusion: </strong>This study delineates a rare yet distinct clinicopathological entity-therapy-related high-grade glioma, which may arise from the complex interplay of prior radiotherapy, chemotherapy, and underlying genetic susceptibility. Recognition of this multifactorial etiology is critical for risk stratification and long-term surveillance.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13365092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interpretable model based on unenhanced MRI radiomics and clinical features for the identification of HER2 expression in breast cancer.","authors":"Mengyi Shen, Dingyi Zhang, Xin Huang, Xin He, Li Zhang, Xiaohua Huang","doi":"10.1007/s12672-026-05560-6","DOIUrl":"10.1007/s12672-026-05560-6","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a model combining unenhanced MRI radiomics and clinical features for identifying HER2-low and HER2-overexpressing breast cancer. SHapley Additive exPlanations (SHAP) was used to interpret the model.</p><p><strong>Methods: </strong>A total of 182 patients (102 HER2-low and 80 HER2-overexpressing) were retrospectively analyzed and split 7:3 into training (n = 127) and test (n = 55) sets. Radiomics features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) maps, and dynamic contrast-enhanced MRI (DCE-MRI), with the optimal features selected. The top-performing radiomics model was integrated with significant clinical features to establish the combined model. Model performance was assessed by area under the curve (AUC), with DeLong's test employed for AUC comparisons. SHAP was used to interpret feature contributions.</p><p><strong>Results: </strong>The T2WI, ADC, and DCE radiomics models achieved training/test set AUCs of 0.693/0.647, 0.675/0.633, and 0.698/0.619, respectively. The T2WI + ADC radiomics model achieved the highest performance, with AUCs of 0.794 in the training set and 0.761 in the test set. Edema demonstrated significant clinical between-group differences (P = 0.044). The combined model integrating radiomics features from the T2WI + ADC model with edema achieved peak AUC values of 0.819 and 0.806, respectively. DeLong's test confirmed the combined model's superiority over the T2WI (P = 0.007, 0.032), ADC (P = 0.002, 0.019), and DCE (P = 0.016, 0.025) models in the training and test sets. ADC-derived MaximumProbability emerged as the most influential radiomics predictor.</p><p><strong>Conclusion: </strong>The combined model integrating radiomics of T2WI and ADC maps with edema demonstrates potential as a non-invasive, contrast-free imaging approach for differentiating HER2-low and HER2-overexpressing statuses, identifying candidates for HER2-targeted therapies. SHAP enhances the interpretability of the model.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430029","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":"A machine learning-guided epithelial plasticity score refines prognostication and immune-context stratification in muscle-invasive bladder cancer.","authors":"Difei Yu, Yu Zhang, Jiarun Tang, Jing Qing, Ke Hu, Jiamo Zhang","doi":"10.1007/s12672-026-05555-3","DOIUrl":"10.1007/s12672-026-05555-3","url":null,"abstract":"<p><strong>Purpose: </strong>Muscle-invasive bladder cancer (MIBC) remains biologically heterogeneous, and clinicopathological variables do not fully capture epithelial-state remodeling linked to progression and treatment response. We developed an epithelial plasticity-related risk score (EPRS) and evaluated its prognostic, biological, and immunological relevance.</p><p><strong>Methods: </strong>Using 368 primary TCGA-MIBC cases, we built a basal-luminal plasticity axis and integrated differential expression, correlation with the continuous plasticity index, and survival association to define 331 candidate genes. Consensus clustering, weighted gene co-expression network analysis, and 10 modeling strategies were used for subtype discovery and score development. EPRS was externally validated in GSE32894 and GSE13507 and further characterized by enrichment analysis, immune deconvolution, single-cell RNA sequencing, immunotherapy-related analyses, and nomogram construction.</p><p><strong>Results: </strong>Two stable plasticity-associated subtypes showed distinct overall survival. WGCNA identified opposing lipid-metabolic and extracellular-matrix/injury-response programs. Among portable models, the Ridge-based EPRS showed the most stable cross-cohort performance and significantly stratified survival in TCGA-MIBC, GSE32894, GSE13507, and the pooled meta cohort. High-EPRS tumors were enriched for extracellular-matrix remodeling, inflammatory signaling, stromal expansion, and an immune-evasive microenvironment despite increased checkpoint-related expression. Single-cell analysis linked EPRS to a continuous malignant epithelial-state landscape. An EPRS-based nomogram improved individualized survival estimation.</p><p><strong>Conclusions: </strong>EPRS captures a clinically relevant epithelial plasticity axis in MIBC and links poor outcome to stromal-immune remodeling and malignant epithelial-state organization.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of RNA binding proteins targeting TP53, RB1 and PTEN in colorectal cancer as potential biomarkers for diagnosis, drug resistance, sensitivity and prognosis.","authors":"Ava Asadi, Mehrdad Hashemi, Maryam Peymani, Najmeh Ranji, Maliheh Entezari","doi":"10.1007/s12672-026-05587-9","DOIUrl":"https://doi.org/10.1007/s12672-026-05587-9","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy with high incidence and mortality. Dysregulated RNA-binding proteins (RBPs) have been implicated in various cancers, yet their role in regulating tumor suppressors in CRC is underexplored. This study analyzed TCGA gene expression data to identify prognostic markers and used CLIP-seq data to uncover RBPs putatively binding to TP53, RB1, and PTEN. Functional enrichment via Gene Ontology (GO) and MSigDB Hallmark pathways suggested involvement in mRNA processing, Myc Targets V1, and Unfolded Protein Response. Univariate Cox regression analyses identified high expression of NOP56, EIF4A3, and IGF2BP1 as associated with poor survival, while high RBM47 expression was linked to improved prognosis; these findings were validated using Kaplan-Meier survival curves. However, multivariate Cox regression analysis was not performed, and independent prognostic validation is required. ROC analysis further indicated that several RBPs could distinguish tumor from normal tissues. Importantly, these AUC values were derived from the TCGA discovery dataset and require independent external validation before any diagnostic application can be considered. Drug sensitivity analyses using GDSC and CCLE datasets revealed exploratory and unadjusted associations between elevated NOP56, FBL, and FUS expression and increased sensitivity to Irinotecan, Nilotinib, and Raf265. A multi-cohort integrated analysis and qRT-PCR confirmed upregulation of selected RBPs in CRC tissues and cell lines. Importantly, these CLIP-seq interactions reflect physical binding potential rather than direct functional regulation of target gene expression. Overall, 22 RBPs were identified as candidate binding-associated regulators of key tumor suppressors, and seven RBPs involved in prominent pathways were identified as candidate prognostic biomarkers requiring further validation in independent cohorts before any clinical application can be considered in CRC, although these findings remain exploratory and require further functional validation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435507","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":"Construction and multi-omics validation of a five-gene ferroptosis-based model for predicting prognosis and therapy response in pancreatic ductal adenocarcinoma with immune landscape analysis.","authors":"Wei Liu, Yifen Shen, Li Rao, Zhenguo Qiao, Xin Ling, Long Cheng, Genhai Shen","doi":"10.1007/s12672-026-05566-0","DOIUrl":"10.1007/s12672-026-05566-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ferroptosis is an iron-dependent programmed cell death, which plays a complex role in pancreatic ductal adenocarcinoma (PDAC), regulating both tumor development and immune interaction. However, the clinical significance and potential molecular mechanism of ferroptosis in PDAC have not been fully clarified, which limits its application in treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In order to identify ferroptosis-related genes (FRGs), we integrated transcriptome data from TCGA-PDAC and GTEx databases, as well as supplementary data from three GEO datasets (GSE62452, GSE78229 and GSE183795). We constructed a prognostic risk model by sequential analysis, which included univariate Cox regression, LASSO regression and multivariate Cox regression. Through Kaplan-Meier survival curve, time-specific ROC curve analysis and correlation study with clinicopathological features, we strictly evaluated the prediction accuracy and clinical relevance of this model. Multi-omics analyses included GO/KEGG/GSEA/GSVA pathway enrichment, CIBERSORT immune deconvolution, ESTIMATE scores, TIDE/ICB response prediction, tumor mutational burden (TMB) profiling, oncoPredict drug sensitivity estimation, single-cell RNA-seq (GSE212966), spatial transcriptome (GSM8452850), pseudotime trajectory, and HPA immunohistochemistry validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A robust five-gene ferroptosis-related prognostic signature (BCAR3, GSK3B, STAT1, MAGED2, MYEOV) was established. Patients categorized into the high-risk group demonstrated a markedly inferior overall survival compared to those in the low-risk group across both the TCGA cohort (5-year AUC = 0.87) and three external validation cohorts (5-year AUC 0.804-0.833). High-risk tumors showed enrichment in mitotic spindle, PI3K-AKT-mTOR, G2M checkpoint, glycolysis, and p53 pathways, markedly elevated KRAS/TP53 mutation rates, higher TMB, an \"inflammatory yet immunosuppressive\" microenvironment (increased resting NK cells/plasma cells, decreased activated NK cells, upregulated checkpoints including CD44/HHLA2/LGALS9), and differential chemotherapy sensitivity (greater sensitivity to gemcitabine, erlotinib, gefitinib, trametinib in high-risk group). Single-cell and spatial analyses confirmed predominant expression in malignant ductal cells, with dynamic pseudotime-dependent patterns (especially GSK3B upregulation in late-stage cells) and enhanced MIF signaling-mediated crosstalk in high-score subpopulations. Protein-level heterogeneity was verified by HPA-IHC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In this study, a concise and externally validated five-gene ferroptosis-related prognostic signature was developed, which effectively stratifies survival outcomes in PDAC patients and reflects ferroptosis-associated alterations in tumor proliferation, metabolic reprogramming, immune evasion, and drug response. This model provides a framework for mechanism-informed precision treatment strategies, such as fer","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430105","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 PTPN6-THBS1 axis drives immunosuppression in renal cell carcinoma by polarizing M2 tumor-associated macrophages.","authors":"Dingkun Hou, Lijuan Kang, Lili Wang, Hongzheng Li, Kaibin Wang, Wei Huang, Changying Li, Haitao Wang","doi":"10.1007/s12672-026-05575-z","DOIUrl":"https://doi.org/10.1007/s12672-026-05575-z","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is characterized by a complex and highly heterogeneous tumor microenvironment (TME), the regulation of which remains incompletely understood. This study systematically investigated the role of protein tyrosine phosphatase non-receptor type 6 (PTPN6) in RCC. Through integrated bioinformatics analysis of TCGA and GEO datasets, we found PTPN6 was consistently overexpressed in multiple cancers, including clear cell (KIRC) and papillary (KIRP) RCC subtypes, where it served as a robust diagnostic marker. Elevated PTPN6 specifically correlated with advanced stage, metastasis, and poor survival exclusively in KIRC. Functional assays in renal carcinoma cells revealed that PTPN6 knockdown minimally affected short-term migration but modestly reduced long-term clonogenic potential. Critically, PTPN6 expression strongly correlated with an immunosuppressive TME signature, enriched stromal/immune scores, and infiltration of M2 macrophages and Tregs. In vitro co-culture experiments and transcriptome sequencing established a mechanistic axis whereby PTPN6 in tumor cells promotes M2 macrophage polarization via upregulation of thrombospondin 1 (THBS1). Furthermore, high PTPN6 expression defined a coherent immunosuppressive landscape and identified a patient subgroup (high PTPN6/low cytolytic activity) with the worst prognosis. Finally, PTPN6 expression was linked to distinct drug sensitivity profiles, and in silico docking supported its potential as a direct pharmacological target. In conclusion, our work establishes PTPN6 as a multifaceted promoter of immunosuppressive microenvironment remodeling and a pivotal regulator of the TME in RCC, positioning it as a promising prognostic marker and a new therapeutic target.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430043","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":"Mechanistic and translational nanomaterial-based strategies for targeting cancer stem cell resistance.","authors":"Karthik K Karunakar, Sowmiya Philips, Nandhini Jayaprakash","doi":"10.1007/s12672-026-05497-w","DOIUrl":"https://doi.org/10.1007/s12672-026-05497-w","url":null,"abstract":"<p><p>Therapeutic resistance remains a major barrier in cancer control and is increasingly recognized as a cancer stem cell (CSC)-driven process rather than a result of residual tumor survival. CSCs sustain tumor initiation, progression, and recurrence through coordinated intrinsic and extrinsic mechanisms, including enhanced drug efflux, cellular quiescence, hypoxia tolerance, efficient DNA damage repair, metabolic adaptation, and phenotypic plasticity. These features render CSCs largely refractory to conventional chemotherapy, radiotherapy, and many molecularly targeted therapies. Although extensive efforts have focused on inhibiting CSC-associated signaling pathways, such as Wnt/β-catenin, Notch, Hedgehog, and PI3K/AKT/mTOR, clinical translation has been limited by pathway redundancy, compensatory signaling, poor tumor penetration, and systemic toxicity. Nanomaterial-based therapeutic platforms represent a promising investigational strategy with potential to address these limitations enabling multi-level intervention against CSC survival architectures. Rationally engineered nanomaterials-including metallic, carbon-based, MXene, and polymeric nanocarriers-enable multi-functional targeting of cancer stem cell resistance by enhancing intracellular delivery, modulating hypoxic niches, and inducing catalytic or photothermal cytotoxicity. These platforms integrate controlled release, ligand-mediated targeting, and microenvironment responsiveness to overcome efflux, quiescence, and repair-mediated survival pathways in CSCs. Nanomaterials bypass ATP-binding cassette transporter-mediated drug efflux, induce cell-cycle-independent cytotoxicity, remodel hypoxic niches, overwhelm DNA repair capacity, and constrain phenotypic plasticity through coordinated pathway modulation. Photothermal and catalytic nanomaterials reduce or eliminate quiescent CSC populations. while ligand-functionalized nanocarriers targeting CSC markers such as CD44, CD133, and EpCAM enhance selective delivery and intracellular drug retention. This review integrates advances in CSC biology with emerging nanomaterial-based strategies and discusses translational challenges and future directions for achieving durable cancer control through CSC-targeted nanotherapy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435597","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":"Cellular reprogramming and signaling control by kaempferol in colorectal cancer.","authors":"Bo Wu, Li-Li Qiu, Yuan Bu, You-Long Liang, Yuan-Yuan Tan","doi":"10.1007/s12672-026-05106-w","DOIUrl":"10.1007/s12672-026-05106-w","url":null,"abstract":"<p><p>Drug resistance and toxicity are major challenges for colorectal cancer (CRC) therapy. Kaempferol (KMP), a natural flavonoid compound, is characterized by low toxicity and multi-targeted effects. KMP has multiple biological functions (anti-inflammation, antioxidation, anti-angiogenesis, apoptosis induction, and immunoregulation). Therefore, KMP is extensively investigated the treatment of various diseases, including cancer. Currently, a series of studies has explored the potential anti-cancer role in CRC therapy. KMP can inhibit the progression of colitis to CRC. Furthermore, KMP suppresses the proliferation of CRC cells and tumor growth. The mechanisms regulated by KMP are involved in multiple signaling pathways such as the matrix metalloproteinases family, VEGF/VEGFR, Wnt/β-catenin, and PI3K/Akt/mTOR. As a multi-targeted inhibitor, KMP shows its natural advantage in combination therapy and is often defined as a sensitizer or attenuator. However, due to the poor stability, absorption, and bioavailability of KMP, its clinical value is hindered. Nano-based delivery systems can compensate for these shortcomings and boost their therapeutic potential. KMP is a hopeful anticancer flavonol, and this review aims to summarize its anticancer effects, mechanisms, and potential applications in CRC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antineoplastic effect of piperine compared with doxorubicin via suppressing γ-secretase/notch pathway in breast cancer cells.","authors":"Maha M Salem, Hamed A Abosharaf, Marian N Gerges, Mohamed A Abd El-Moneim, Tarek M Mohamed, Aliaa M Radwan","doi":"10.1007/s12672-026-05165-z","DOIUrl":"10.1007/s12672-026-05165-z","url":null,"abstract":"<p><p>Breast carcinoma is the most prevalent and lethal malignancy affecting females, and it always presents an essential healthcare problem. Doxorubicin (DOX) is a common chemotherapy utilized in treating breast carcinoma, but it also has dangerous side effects. Hence, searching for potent and safe anticancer compounds is urgent. An alkaloid, piperine, mostly found in pepper species, is a naturally occurring substance with anticancer properties. This work aims to assess the anticancer impact of piperine on breast carcinoma cells by potentially inhibiting the γ-secretase/Notch pathway, and to compare its impacts with those of DOX. The anti-proliferative effects of piperine and DOX were evaluated on various human breast carcinoma cell lines (MCF-7, T47D, and MDA-MB-231). Additionally, a flow cytometric analysis was carried out to identify the cell cycle arrest. Moreover, the protein expression levels of Notch-1, γ-secretase components, NICD, c-myc, p21, Bax, and Bcl-2 were assessed. The results demonstrated that among the tested cell lines, MDA-MB-231 cells exhibited the highest sensitivity to piperine treatment, with the lowest IC₅₀ value (32.37 ± 2.5 µM). At the G2/M phase, piperine and DOX both stopped the cell cycle. Furthermore, piperine and DOX inhibited the Notch signaling by reducing Notch-1, γ-secretase components, and NICD expression. Piperine and DOX also reduced the levels of Notch target proteins, namely, p21 and c-myc. Lastly, both drugs induced apoptosis by elevating Bax and reducing Bcl-2 expression in malignant breast cells. The promise of piperine as a targeted therapy candidate for the treatment of breast cancer is substantially supported by this research.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}