Oncology Research最新文献

{"title":"Upregulation of Sox2 Following Saracatinib Treatment Contributes to a Resistant Phenotype in Colorectal Cancer Cells under Growth Factor-Supplemented Conditions.","authors":"Chanwoong Yoon, Euihyeon Na, Min Joo Choi, Sang-Pil Yoon","doi":"10.32604/or.2026.074140","DOIUrl":"https://doi.org/10.32604/or.2026.074140","url":null,"abstract":"<p><strong>Objective: </strong>Increased Src kinase activity is known to correlate with cancer progression and poor prognosis, indicating that Src plays a central role in cell migration and invasion. In this study, we investigated the effects of saracatinib, a Src kinase inhibitor, under anoikis-resistant conditions in colorectal cancer cells.</p><p><strong>Methods: </strong>Wild-type and 5-fluorouracil-resistance acquired SNU-C5 colorectal cancer cells were cultured in both monolayer and spheroid systems under fetal bovine serum (FBS) or growth factor (GF) supplemented conditions. Cell viability assay, flow cytometry, wound healing assay, spheroid formation and morphometric analysis, and Western blotting were performed using both adherent cells and spheroids.</p><p><strong>Results: </strong>Saracatinib significantly reduced cell viability and migration in both cell lines, predominantly through the induction of apoptosis. Spheroid formation was less efficient under GF-supplemented conditions than under FBS-supplemented conditions. The anti-cancer effects of saracatinib were mediated through inhibition of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase (ERK), or epidermal growth factor receptor (EGFR) signaling pathways. Although most cancer stem cell (CSC) markers were suppressed by saracatinib, expression of sex determining region Y-box-2 (Sox2) was paradoxically increased in monolayer cultures. Upon re-treatment with saracatinib, Sox2-upregulated cells formed larger spheroids under GF-supplemented conditions compared with wild-type cells.</p><p><strong>Conclusions: </strong>Saracatinib exerts anti-cancer effects in colorectal cancer cells by downregulating MAPKs, EGFR, and CSC-associated markers. However, paradoxical upregulation of Sox2 influenced spheroid formation under GF-supplemented conditions, suggesting that Sox2 may contribute to drug resistance or recurrence in colorectal cancers.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"23"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818700","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":"Bevacizumab and Paclitaxel in Advanced, Hormone Receptor-Positive Breast Cancer: Multifactor Dimensionality Reduction Methodology to Identify Best Overall Survival.","authors":"Luigi Coltelli, Paola Orlandi, Chiara Finale, Gianna Musettini, Luna Chiara Masini, Marco Scalese, Giulia Soria, Elena Sartori, Ylenia Nodari, Giada Arrighi, Arianna Bandini, Marta Banchi, Costanza Tacchi, Donghao Tang, Barbara Salvadori, Lucia Tanganelli, Simona Giovannelli, Mirco Pistelli, Samanta Cupini, Maurizio Lucchesi, Alessandro Cosimi, Giulia Lorenzini, Elisa Biasco, Chiara Caparello, Giulia Acconci, Eloise Fontana, Eleonora Bona, Azzurra Farnesi, Antonio Pellino, Andrea Marini, Ermelinda De Maio, Irene Stasi, Cecilia Barbara, Enrico Sammarco, Javier Rosada, Giacomo Allegrini, Guido Bocci","doi":"10.32604/or.2026.073799","DOIUrl":"https://doi.org/10.32604/or.2026.073799","url":null,"abstract":"<p><strong>Background: </strong>The treatment of advanced hormone receptor-positive (HR+) breast cancer has seen relevant changes in last years. However, bevacizumab remains an option when combined with paclitaxel, but no certified pharmacogenetic profiles are now usable for the prediction of its response in breast cancer patients. This study aimed to explore the pharmacogenetic interactions among single nucleotide polymorphisms (SNPs) of genes involved in the angiogenic process and their impact on progression-free survival (PFS) and overall survival (OS) in hormone receptor-positive (HR+) metastatic breast cancer subjects administered with bevacizumab plus paclitaxel, or with paclitaxel alone (clinicaltrial.gov identifier NCT01935102).</p><p><strong>Methods: </strong>Germline DNA extracted from blood samples was analyzed using real-time polymerase chain reaction to investigate SNPs. The multifactor dimensionality reduction (MDR) analysis was employed to assess interactions between these genetic variants. A total of 168 eligible patients were analyzed. Among these, 106 patients received both paclitaxel and bevacizumab, while 62 received paclitaxel alone.</p><p><strong>Results: </strong>In the combination therapy group, MDR analysis identified two pharmacogenetic interaction profiles involving specific genotypes of vascular endothelial growth factor-A(VEGF-A) rs833061 and vascular endothelial growth factor receptor-2 (VEGFR-2) rs1870377. Patients with a favorable genetic profile had a median PFS (mPFS) of 22.9 months, compared to 8.7 months in those with an unfavorable profile (<i>p</i> = 0.001). Cox proportional hazards analysis displayed an adjusted hazard ratio of 0.443 (95% CI: 0.284-0.691; <i>p</i> < 0.0001). The median OS (mOS) was 50.2 months for the favorable profile vs. 23.5 months for the unfavorable (<i>p</i> = 0.003), with an adjusted hazard ratio (HR) of 0.404 (95% CI: 0.249-0.657; <i>p</i> < 0.0001). In the 62 subjects administered with just paclitaxel, no significant differences in PFS (<i>p</i> = 0.820) or OS (<i>p</i> = 0.143) were observed between favorable and unfavorable genetic profiles.</p><p><strong>Conclusions: </strong>The MDR analysis of VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes can detect a subgroup of bevacizumab-administered+ metastatic breast cancer patients with improved PFS and OS.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"13"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818009","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":"CDKN1A/p21 Influences the Survival and Expansion of Breast Cancer Stem Cells after Oxidative Damage.","authors":"Evangelos Manousakis, Cristina Moreta-Moraleda, Clàudia Martinez Miralles, Anna Tomàs Pujolà, Houda Baccara, Laia Liñán Franquet, Montserrat Montañés Albó, Roberto Ferrari, Roni H G Wright","doi":"10.32604/or.2026.074965","DOIUrl":"https://doi.org/10.32604/or.2026.074965","url":null,"abstract":"<p><strong>Objective: </strong>Breast cancer remains one of the most prevalent malignancies among women worldwide, and despite advances in therapy and treatment options, tumour relapse and metastasis remain major clinical challenges, largely driven by the breast cancer stem cells (BCSCs) niche that resists conventional treatments and regenerates tumours. In breast cancer, where approximately 30% of patients who initially respond to treatment ultimately relapse and die of metastatic disease, targeting BCSCs is critical for improving patient outcomes. Cyclin-dependent kinase inhibitor 1A/p21 (CDKN1A/p21) is a multifunctional protein that is known primarily for its role in regulating the cell cycle in response to DNA damage. However, in this study, we aimed to explore the role of CDKN1A/p21 in the survival and expansion of BCSCs.</p><p><strong>Methods: </strong>We used three-dimensional <i>in vitro</i> models to assess the influence of CDKN1A/p21 expression on the survival of BCSCs both under basal conditions and after oxidative damage. Spatial transcriptomics analysis and chromatin immunoprecipitation-quantitative PCR (qPCR) were used to investigate the role of CDKN1A/p21 in the regulation and control of BCSC gene expression signatures.</p><p><strong>Results: </strong>We demonstrated that alterations in CDKN1A/p21 expression affect the ability of breast cancer cells to grow and survive after oxidative damage. Mechanistically, we found that CDKN1A/p21 directly binds to the promoter and regulates the expression of CD44, SPP1, and TMSB10, a combination gene signature that is associated with a greater probability of recurrence and metastasis in breast cancer patients.</p><p><strong>Conclusions: </strong>We propose that changes in gene regulation mediated by CDKN1A/p21 possibly contribute to cancer stem cell survival after oxidative damage, thus making CDKN1A/p21 a promising target for future drug discovery projects aimed at addressing the issue of therapeutic resistance and breast cancer metastasis.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"20"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818049","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":"Elevated C-Reactive Protein as a Potential Biomarker for Neurological Adverse Events in Immune Checkpoint Inhibitor Therapy: A Prospective Cohort Study.","authors":"Laura Duzzi, Nora Möhn, Emily Narten, Janin Thomas, Susann Mahjoub, Lea Grote-Levi, Konstantin Jendretzky, Sandra Nay, Felix Konen, Jonas Wiegmann, Gernot Beutel, Tabea Fröhlich, Benjamin-Alexander Bollmann, Thomas Wirth, Imke von Wasielewski, Florian H Heidel, Ralf Gutzmer, Thomas Skripuletz, Philipp Ivanyi","doi":"10.32604/or.2026.074095","DOIUrl":"https://doi.org/10.32604/or.2026.074095","url":null,"abstract":"<p><strong>Objectives: </strong>Since 2011, immune checkpoint inhibitors (ICI) have transformed the treatment of various cancers. However, our understanding of the autoimmune adverse events, particularly those affecting the nervous system, remains limited. These adverse events can cause significant disability or even death, yet there are currently no established guidelines or biomarkers to aid diagnosis and treatment. With this study, we aim to gain a deeper understanding of neurological adverse events and investigate potential predictive biomarkers.</p><p><strong>Methods: </strong>Between 19 December 2019 and 21 August 2021, 150 out of 543 ICI-treated cancer patients were eligible for our prospective monocentric cohort study. Neurological assessments, clinical scores and the severity of side effects were analysed. Blood samples were taken before, during and after therapy. Patients with neurological AEs (the nAE group) and those without (the non-nAE group) were compared to identify potential predictive markers.</p><p><strong>Results: </strong>Of the 150 patients, 55 (36.7%) experienced nAE of any kind or severity, ranging from non-specific neurological symptoms to severe events. Severe nAE (Grade ≥ 3) was observed in 3.3% of patients and included cases of encephalitis and cerebral vasculitis. Regarding potential biomarkers, an increase in C-reactive protein (CRP) within the first 3-4 weeks was statistically associated with an increased likelihood of nAE in this study. As for patient- and treatment-related parameters, concurrent chemotherapy was found to be significantly associated with the occurrence of nAE.</p><p><strong>Conclusions: </strong>This study observed a relatively high rate of nAE under ICI therapy, partly due to the intentionally broad case definition. CRP elevation emerged as a potential predictive biomarker, warranting further investigation. However, other statistically significant markers did not consistently demonstrate clinical relevance.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"17"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818296","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":"Elucidating the Potential Targets and Mechanisms of Bisphenol A-Induced Prostate Cancer Based on Network Toxicology and Molecular Docking Analyses.","authors":"Ashuai Du, Dianbin Guo, Dongbo Yuan, Kai Li, Yuanyuan Luo, Songsong Tan, Xuchao Dai, Bo Yu, Wanxiang You, Junjie Zhao, Bo Yan, Kehua Jiang, Xiaofei Fan, Jianguo Zhu","doi":"10.32604/or.2026.076716","DOIUrl":"https://doi.org/10.32604/or.2026.076716","url":null,"abstract":"<p><strong>Background: </strong>Bisphenol A (BPA) is a widely used industrial chemical and endocrine-disrupting compound, and accumulating evidence suggests that it may contribute to prostate cancer progression; however, the underlying molecular mechanisms remain incompletely elucidated. This study aimed to elucidate the molecular targets and signaling pathways underlying BPA-induced prostate cancer progression.</p><p><strong>Methods: </strong>In this study, an integrated strategy combining network toxicology, molecular docking, and molecular dynamics simulations was employed to identify potential BPA-related targets and signaling pathways involved in prostate cancer. Candidate targets were retrieved from public databases, followed by protein-protein interaction network analysis to screen key hub genes. Functional assays were performed to evaluate the effects of BPA on prostate cancer cell migration, invasion, epithelial-mesenchymal transition (EMT), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling, and an <i>in vivo</i> mouse model was used to assess the impact of BPA exposure and PI3K inhibition on tumor progression.</p><p><strong>Results: </strong>Eighteen BPA-related core targets were identified, among which androgen receptor (AR), matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), kallikrein-related peptidase 3 (KLK3), and hypoxia-inducible factor 1 alpha (HIF1A) emerged as key hub genes. Computational analyses indicated stable predicted interactions between BPA and these proteins. Functionally, BPA exposure promoted prostate cancer cell invasion and EMT, which were associated with activation of the PI3K/AKT and MMP signaling pathways, whereas the PI3K inhibitor LY294002 effectively attenuated BPA-induced invasive phenotypes <i>in vitro</i> and reduced tumor progression <i>in vivo</i>.</p><p><strong>Conclusions: </strong>Collectively, these findings provide mechanistic insights into BPA-driven prostate cancer progression and highlight the value of network toxicology-based approaches in environmental toxicology research.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"35"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818396","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":"MYO18A Expression is a Prognostic Factor for Progression-Free Survival in Grade 4 Adult gliomas. Preliminary Report.","authors":"Aleksander Strąk, Ludmiła Grzybowska-Szatkowska, Paweł Cisek, Marta Ostrowska-Leśko, Jarosław Dudka, Joanna Kubik, Jacek Osuchowski, Paweł Szmygin, Bożena Jarosz, Andrzej Krajka, Tomasz Krajka, Kazimierz Szatkowski, Brygida Ślaska","doi":"10.32604/or.2026.074078","DOIUrl":"https://doi.org/10.32604/or.2026.074078","url":null,"abstract":"<p><strong>Objectives: </strong>Brain gliomas are among the tumors with the worst prognosis, and their incidence is increasing. Postoperative temozolomide-based chemoradiotherapy for grades 3 and 4 gliomas extended overall survival (OS) by approximately two months. An increasing number of clinical trials are investigating molecular-based therapy. Recent studies have demonstrated the involvement of Golgi apparatus proteins, including MYO18A (myosin-18A), in processes associated with abnormal proliferation, migration, apoptosis evasion, and angiogenesis promotion. The aim of this study was to investigate whether MYO18A has prognostic value in patients treated for brain gliomas.</p><p><strong>Methods: </strong>The research material in the work included tumor samples taken during neurosurgery and blood samples from 45 patients treated for brain gliomas with grade of 1 to 4 according to WHO, which were used to determine the expression of <i>MYO18A</i> mRNA (messenger ribonucleic acid). Expression of <i>MYO18A</i> was presented as fold changes in RQ (relative quantification) mRNA levels.</p><p><strong>Results: </strong>This study showed higher <i>MYO18A</i> values in patients diagnosed with grade G4 glioma among those with a shorter progression-free survival (PFS) time and those living shorter than the group average. However, statistically significant differences were achieved only for PFS for the <i>MYO18A</i> RQ feature (PFS = 4.64, SD = 2.16 vs. PFS = 15.83 and SD = 7.27, <i>p</i> = 0.0231). Also, a positive correlation was demonstrated between tumor volume and <i>MYO18A</i> expression.</p><p><strong>Conclusion: </strong>The level of expression of <i>MYO18A</i> can be considered a prognostic factor for PFS in patients treated for G4 gliomas, because higher <i>MYO18A</i> expression was associated with earlier recurrence.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"22"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818555","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":"Circ72688 Drives Breast Cancer Invasion and Metastasis via the miR-654-5p/ORAI2 Axis.","authors":"Haojie Yang, Zicong Tan, Zihao Liu, Kang Chen, Ning Liufu, Fengtao Ji","doi":"10.32604/or.2026.073081","DOIUrl":"https://doi.org/10.32604/or.2026.073081","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) play a crucial role in the progression of malignant tumors such as breast cancer.</p><p><strong>Methods: </strong>A circRNA microarray was used to detect key circRNAs in breast cancer. Expression of Circ72688 was verified by quantitative reverse transcription PCR (qRT-PCR) and fluorescence <i>in situ</i> hybridization (FISH) assay. Transwell assay and <i>in vivo</i> assay were conducted to prove the function of Circ72688. Exploring the downstream mechanism, dual-luciferase reporter assay, western blotting, and tissue microarray were performed.</p><p><strong>Results: </strong>We sequenced and identified a circRNA, hsa-circ-0072688, also known as Circ72688. Our research found that Circ72688 enhanced tumor metastasis both <i>in vivo</i> and <i>in vitro</i>. Mechanistically, Circ72688 acted as a molecular sponge for hsa-miR-654-5p, thereby affecting the transcription of ORAI2. The expression levels of Circ72688 and ORAI2 were significantly higher in breast cancer tissues compared to adjacent normal tissues, and a notable positive correlation could be seen between them.</p><p><strong>Conclusions: </strong>In summary, our study demonstrated the critical role of Circ72688 in breast cancer invasion and metastasis, and how Circ72688 partially regulated ORAI2 through hsa-miR-654-5p. Targeting Circ72688 might be a potential therapeutic strategy for breast cancer.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"33"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818107","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":"Data Mining for Identification of Targets and Repurposed Drugs to Eliminate Persistent Chronic Myeloid Leukaemia Stem Cells: Targeting RAS/RAF Signalling.","authors":"I Made Bayu Anggriawan, Heather G Jørgensen","doi":"10.32604/or.2026.074734","DOIUrl":"https://doi.org/10.32604/or.2026.074734","url":null,"abstract":"<p><strong>Background: </strong>Persistent leukaemic stem cells (LSCs) in chronic myeloid leukaemia (CML) are insensitive to targeted tyrosine kinase inhibitors (TKIs). Identifying alternative molecular vulnerabilities may offer new therapeutic opportunities. This study aimed to identify active RAS/RAF signalling pathway components in persistent CML-LSCs using publicly available datasets to propose a novel drug combination that could synergise with TKI therapy.</p><p><strong>Methods: </strong>EMBL-EBI Single Cell Expression Atlas and Stemformatics were used to analyse gene expression within the chosen signalling pathway using DESeq2 analysis in R Studio. Genes that showed statistically significant differences across three comparisons (CML vs. normal; post vs. pre TKI; post TKI vs. normal) were evaluated for gene dependency (Chronos scores), expression profiles, and inhibitor sensitivity using the DepMap platform, with a focus on CML cell lines. Candidate inhibitors were identified using DrugBank.</p><p><strong>Results: </strong><i>PPP2CA</i> demonstrated broad essentiality with negative Chronos scores consistent with strong gene dependency. Its expression was consistently high, reinforcing its biological relevance in CML. LB-100 was found as a PP2A inhibitor under trial. Sensitivity analysis revealed LB-100 affected 548 cancer cell lines broadly.</p><p><strong>Conclusion: </strong><i>PPP2CA</i> represents a promising therapeutic vulnerability in CML, supported by both strong dependency and consistent expression in myeloid models, while BRAF showed limited relevance outside mutation-driven cancers. Variation in experimental platforms, sample representation, and data integration across public datasets is a recognised study limitation. Nonetheless, LB-100 may provide a novel therapeutic avenue in CML, provided further preclinical functional and clinical validation is performed in patient-derived samples to confirm translational applicability of the findings.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"14"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818244","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":"Integrated Global Phosphoproteomic, Bioinformatic, and Machine Learning Analysis Reveals Regulatory Networks of TOP1, TOP2A, TOP2B, and C1orf35 in Hepatocellular Carcinoma (HCC).","authors":"Aktham Mestareehi","doi":"10.32604/or.2026.073745","DOIUrl":"https://doi.org/10.32604/or.2026.073745","url":null,"abstract":"<p><strong>Objective: </strong>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, largely due to late diagnosis, molecular heterogeneity, and limited prognostic biomarkers. Aberrant protein phosphorylation plays a critical role in cancer progression by regulating DNA damage response, cell cycle control, and signaling pathways; however, the prognostic relevance of phosphorylation events in key DNA topology-related proteins remains incompletely understood. This study aimed to investigate the prognostic significance of phosphorylation of TOP1, TOP2A, TOP2B, and C1orf35 in HCC and to characterize their associated molecular features to identify potential diagnostic and therapeutic biomarkers.</p><p><strong>Methods: </strong>Publicly available HCC phosphoproteomic and proteomic datasets were analyzed to identify significantly upregulated phosphorylation sites of TOP1, TOP2A, TOP2B, and C1orf35. Integrated bioinformatics and machine learning approaches were applied, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) network analysis, drug-gene interaction analysis, and survival analyses (overall and disease-free survival).</p><p><strong>Results: </strong>A total of 11,547 phosphorylation sites corresponding to 4043 phosphoproteins were quantified from 159 HCC patients. Phosphorylation of TOP1, TOP2A, TOP2B, and C1orf35 was significantly upregulated. Enriched pathways included DNA damage response, homologous recombination repair, cell cycle regulation, SUMOylation, and TP53 signaling. PPI analysis identified these proteins as highly interconnected hub nodes. Elevated expression was significantly associated with poor clinical outcomes.</p><p><strong>Conclusions: </strong>Phosphorylated TOP1, TOP2A, TOP2B, and C1orf35 are strongly associated with HCC progression and poor prognosis, highlighting their potential as prognostic biomarkers and therapeutic targets. These insights not only enhance our understanding of the complex molecular mechanisms underlying HCC but also offer promising avenues for the identification of novel therapeutic targets.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"18"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818495","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":"Isoliquiritigenin Impedes Breast Cancer Progression through PITX1-PFKP-Mediated Glycolysis Reprogramming.","authors":"Cong Liu, Zhenyu Zhang, Ronghua Feng, Mengsi Zeng, Hui Li, Mei Zhu, Lan Zhuang, Zongjuan Li, Tao Wu","doi":"10.32604/or.2026.077059","DOIUrl":"https://doi.org/10.32604/or.2026.077059","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the leading cause of cancer-related deaths in women, primarily due to distant metastasis. Metabolic reprogramming plays a critical role in tumor growth and spread, but the metabolic mechanisms underlying metastasis in breast cancer remain unclear. The primary objective of this study is to identify molecular targets mediating breast cancer progression and to evaluate whether targeting the metabolic reprogramming represents a potential therapeutic strategy.</p><p><strong>Methods: </strong>To uncover key metabolic regulators involved in breast cancer progression, we analyzed high-throughput RNA sequencing data and identified Paired Like Homeodomain 1 (PITX1) as a frequently upregulated oncogene. Its expression was further validated by immunohistochemistry, quantitative PCR, and western blotting across various metastatic breast cancer tissues. The correlation between PITX1 expression and patient survival was also evaluated. Functional assays were conducted to explore the role of PITX1 in promoting breast cancer proliferation and metastasis. As this study is primarily based on mechanistic cellular and bioinformatic analyses rather than clinical intervention trials, traditional clinical effect size metrics are not directly applicable. However, we have now ensured that all major findings include quantitative effect measurements (e.g., fold changes, hazard ratios where applicable, correlation coefficients) together with corresponding statistical significance values to improve clarity and transparency.</p><p><strong>Results: </strong>Elevated PITX1 expression was significantly associated with poorer overall survival, distant metastasis-free survival, relapse-free survival, and post-progression survival in breast cancer patients. Silencing PITX1 significantly reduced breast cancer cell proliferation and suppressed glycolysis. Mechanistically, we found that PITX1 transcriptionally activates Phosphofructokinase platelet (PFKP), a key glycolytic enzyme, thereby enhancing glycolytic flux to promote tumor growth and metastatic capacity. Notably, isoliquiritigenin was identified as a small-molecule inhibitor that targets the PITX1-PFKP axis, downregulating glycolysis and consequently suppressing breast cancer progression.</p><p><strong>Conclusion: </strong>Our findings uncover a novel oncogenic mechanism by which PITX1 promotes breast cancer progression and metastasis through glycolytic reprogramming. Targeting the PITX1-PFKP axis with isoliquiritigenin offers a promising therapeutic strategy for breast cancer treatment.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 5","pages":"36"},"PeriodicalIF":4.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818500","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}