Oncology Research最新文献

{"title":"Epigenomic and Metabolic Interplay in the Development of Metastatic Brain Tumors.","authors":"Vishal Rastogi, Deepak Verma, Saurabh Verma, Prakash Haloi, Shruti Kapoor, Havagiray R Chitme, Nethaji Muniraj, Priyanka Saroj","doi":"10.32604/or.2026.072620","DOIUrl":"10.32604/or.2026.072620","url":null,"abstract":"<p><p>Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment. Hypoxia-inducible factor-1α (HIF1α) enhances glycolytic flux, lactate accumulation, and histone lactylation, collectively supporting metastatic colonization and immune evasion. Key metabolites including acetyl-CoA, S-adenosylmethionine (SAM), α-ketoglutarate (α-KG), fumarate, and 2-hydroxyglutarate (2-HG)-directly modify chromatin states by regulating histone acetyltransferases, DNA/histone methyltransferases, and α-KG dependent dioxygenases such as Ten-Eleven Translocation (TET) enzymes and lysine demethylases (KDMs). These metabolic shifts result in aberrant DNA methylation, histone lysine residue at position 27 on Histone H3 (H3K27) trimethylation, and depletion of 5-hydroxymethylcytosine (5hmC), all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System (CNS) tumors. Additionally, the blood-brain barrier (BBB) and blood-tumor barrier (BTB) impose nutrient restrictions and induce metabolic dependency on glutamine, acetate, and lactate shuttling, thereby reshaping epigenetic enzyme activity. We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity, stemness, and therapeutic resistance. Understanding these coupled pathways reveals vulnerable nodes such as HIF1α signaling, α-KG-dependent demethylation, and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors. The present review aims to provide in-depth insights into epigenetic regulation, including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming, highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"7"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378259","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":"Interplay of Interleukin-1<b>β</b> and Curcumin on VEGF Expression in Breast Cancer Cells.","authors":"Norbert Nass, Atanas Ignatov, Thomas Kalinski","doi":"10.32604/or.2025.072793","DOIUrl":"10.32604/or.2025.072793","url":null,"abstract":"<p><strong>Objectives: </strong>Vascular endothelial growth factor (VEGF) regulates tumor vascularization in response to hypoxia and inflammatory signals. The polyphenol curcumin is supposed to interfere with inflammation-induced VEGF secretion and might therefore support anti-VEGF-based treatments. We aimed to investigate the interaction between curcumin and the inflammatory cytokine Interleukin-1β (IL-1β) for VEGF secretion in breast cancer cell lines representing major breast cancer subtypes.</p><p><strong>Methods: </strong>VEGF in cell cultures was detected by Western blot and enzyme-linked immunosorbent assay (ELISA). Kinase phosphorylation was investigated by Western blotting. Gene expressions were analyzed by correlation tests. VEGF was evaluated in a retrospective breast cancer cohort by immunohistochemistry. Survival analysis was performed by the Kaplan-Meier algorithm.</p><p><strong>Results: </strong>VEGF secretion and kinase signaling in response to IL-1β and curcumin varied significantly for the cell lines MCF-7 (Luminal A), SK-BR-3 (HER2/neu+), MDA-MB-231, and UACC-3199 (triple negative breast cancer). All cell lines increased VEGF secretion under hypoxia, but IL-1β increased VEGF secretion only in MCF-7 cells. Curcumin inhibited VEGF secretion in MDA-MB-231, but increased it in MCF-7 and UACC-3199 cells. Curcumin induced phosphorylation of extracellular signal-regulated kinase (ERK) and p38-mitogen-activated protein kinase (p38-MAPK). However, inhibitor experiments demonstrated that ERK was more important for VEGF secretion. In gene expression data from the METABRIC study, no clear correlation of hypoxia-induced factor (HIF1A), IL-1β, and VEGF mRNA expression was observed; however, a suggested crosstalk of hypoxia and inflammatory pathways was observed.</p><p><strong>Conclusion: </strong>These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with anti-VEGF, anti-IL-1β, or curcumin will also vary within breast cancers.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"13"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378082","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":"Advances in Targeted and Immunotherapy for High-Risk Cutaneous Malignancies.","authors":"Amy J Petty, Drew A Emge, Adela R Cardones","doi":"10.32604/or.2025.073383","DOIUrl":"https://doi.org/10.32604/or.2025.073383","url":null,"abstract":"<p><p>Skin cancer remains the most commonly diagnosed malignancy worldwide, with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma representing the most clinically significant types. While traditional treatments are effective for early-stage disease, advanced or metastatic cases often pose significant therapeutic challenges. Patients with high-risk or recurrent disease face limited options and poor prognoses. The emergence of immunotherapy has dramatically transformed the treatment landscape across multiple cancer types, including cutaneous malignancies. This review highlights recent advancements in immunotherapeutic strategies for BCC, cSCC, and melanoma, underscoring their growing importance in dermatologic oncology. We synthesize current evidence and ongoing clinical trials for immunotherapy across these three skin cancer types. We also explore the molecular mechanisms underpinning immune responsiveness and potential biomarkers of response. As immunotherapy continues to expand within dermatology, understanding its role, limitations, and future directions is essential for optimizing patient care. The integration of immunotherapy into dermatologic practice represents not only a therapeutic innovation but also a shift toward precision medicine in cutaneous oncology.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"2"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378087","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":"<i>miR-449a</i>: A Novel Biomarker for Diagnosis, Prognosis, and Treatment Response in Locally Advanced Laryngeal Squamous Cell Carcinoma.","authors":"Amal F Gharib, Ohud Alsalmi, Hayaa M Alhuthali, Afaf Alharthi, Saud Ayed Alharthi, Shaimaa A Alharthi, Rasha L Etewa, Wael H Elsawy","doi":"10.32604/or.2025.073051","DOIUrl":"10.32604/or.2025.073051","url":null,"abstract":"<p><strong>Background: </strong>Locally advanced laryngeal squamous cell carcinoma (LA-LSCC) presents clinical challenges due to the lack of reliable non-invasive biomarkers. This study aimed to evaluate <i>miR-449a</i> as a diagnostic and prognostic biomarker in LA-LSCC. Methods: <i>miR-449a</i> expression was analyzed in tumor tissues, adjacent normal tissues, and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We assessed the diagnostic accuracy by Receiver Operating Characteristic curve (ROC curves), clinicopathological associations, survival outcomes (Kaplan-Meier), and treatment response dynamics.</p><p><strong>Results: </strong><i>miR-449a</i> was significantly downregulated in LA-LSCC tissues (<i>p</i> < 0.0001) and serum (<i>p</i> < 0.0001), with a strong tissue-serum correlation (R² = 0.988). Tissue <i>miR-449a</i> demonstrated a diagnostic accuracy (Area Under the Curve, AUC = 0.857), while serum showed moderate accuracy (AUC = 0.734). High <i>miR-449a</i> expression correlated with favorable clinicopathological features and improved survival (median overall survival: 67.82 vs. 23.74 months; <i>p</i> = 0.0012). Multivariate analysis confirmed <i>miR-449a</i> as an independent prognostic factor (<i>p</i> < 0.001). <i>miR-449a</i> levels increased post-treatment, particularly in responders to chemotherapy/radiation (<i>p</i> < 0.0001).</p><p><strong>Conclusion: </strong><i>miR-449a</i> serves as a non-invasive biomarker for LA-LSCC diagnosis, prognosis, and treatment monitoring. Its dynamic expression highlights potential for risk stratification and therapy response prediction, warranting further validation in larger cohorts.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"21"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378060","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":"Ugonin J Inhibits EMT and Migration in Prostate Cancer by Suppressing ADAM9 Expression.","authors":"Jo-Yu Lin, Tien-Huang Lin, Ya-Jing Jiang, Liang-Wei Lin, Kuan-Ying Lai, Yi-Chin Fong, Chih-Chuang Liaw, Chih-Hsin Tang","doi":"10.32604/or.2025.074202","DOIUrl":"10.32604/or.2025.074202","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages. The study aimed to investigate the effects of Ugonin J, a natural compound isolated from <i>Helminthostachys zeylanica</i>, on PCa metastasis.</p><p><strong>Methods: </strong>The effects of Ugonin J on cell motility were assessed using migration and invasion assays. Reverse Transcription Quantitative PCR (RT-qPCR) and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression. RNA sequencing (RNA-seq) analysis was performed to investigate candidate mechanisms. Differential gene expression analysis in PCa patients was conducted using multiple databases.</p><p><strong>Results: </strong>Here, we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability. RNA-seq analysis suggests that epithelial-mesenchymal transition (EMT) is potentially involved in Ugonin J's anti-motility effects. Ugonin J also suppresses the expression of mesenchymal markers N-cadherin, β-catenin, Snail, and Slug while upregulating the expression of the epithelial marker E-cadherin. Furthermore, among 13 A disintegrin and metalloproteinase (ADAM) proteins, A disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) is the most downregulated following Ugonin J treatment, according to our RNA-seq data. Importantly, clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis. Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT, migration, and invasion in PCa cells. Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and nuclear factor-κB (NF-κB) pathways.</p><p><strong>Conclusions: </strong>Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"19"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378187","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":"Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.","authors":"Abhishikt David Solomon, Himanshu Kumar Vats, Shivam Chowdhary, Supriya Nandlal Kanoujiya, Ajit Prakash, Hina Sultana, Sabyasachi Mohanty, Billy W Day, Tarun Pant","doi":"10.32604/or.2026.071632","DOIUrl":"10.32604/or.2026.071632","url":null,"abstract":"<p><p>Tumor survival, genomic stability, and therapy resistance are dictated by the DNA damage response (DDR). Although poly (ADP-ribose) polymerase (PARP) inhibitors have established the DDR as a therapeutic target, many tumors evade first-generation drugs by rewiring their adaptive repair pathways and imposing microenvironmental constraints. This review synthesizes recent discoveries in key DDR pathways, such as PARP, ataxia telangiectasia and Rad3-related kinase (ATR), ataxia telangiectasia mutated kinase (ATM), checkpoint kinase 1 (CHK1), WEE1 G2 checkpoint kinase (WEE1), and DNA-dependent protein kinase (DNA-PK), and describes the next-generation inhibitors designed to increase selectivity and circumvent resistance. We also analyze the role of hypoxia, stromal remodeling, inflammatory cytokines, and immune-cell plasticity in the tumor microenvironment in determining DDR dependency and response. Special attention is paid to cGAS-STING, immunogenic signaling via damage-associated molecular patterns (DAMPs), and mechanisms that convert a cold tumor into a hot one. Lastly, we touch upon the new nanocarrier-based delivery approaches that enhance pharmacokinetics, target resistant tumor niches, and expand the possibilities for combinatorics with immunotherapy and radiotherapy. Collectively, these findings provide a guide to the implementation of next-generation DDR inhibitors and nanomedicines to deliver a more accurate, durable, and context-specific cancer therapy.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"5"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378225","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":"Research on the Mechanism of \"Cold Tumor\" Formation and Immunotherapy for Its Transformation into \"Hot Tumor\".","authors":"Liang Zhou, Jia Zhou, Zhengyi Wang","doi":"10.32604/or.2026.069317","DOIUrl":"10.32604/or.2026.069317","url":null,"abstract":"<p><p>A clear goal in cold tumor research is to identify strategies for converting them into immunologically 'hot' tumors with enhanced immune cell infiltration and activity, thereby improving their responsiveness to immunotherapy. The genesis of cold tumors is exceedingly intricate. In recent times, as the analysis of this phenomenon has been pursued with greater depth, a suite of advanced diagnostic and therapeutic technologies has surfaced. These novel approaches and tactics are anticipated to modulate the tumor immune microenvironment across various dimensions, thereby facilitating the advancement of personalized and precise treatment modalities for cold tumors. The present article addresses the challenge of diminished therapeutic responsiveness to \"cold tumors\" within clinical settings. It systematically elucidates the multi-faceted regulatory mechanisms underlying immune evasion in cold tumors and offers a detailed analysis of advanced therapeutic strategies that incorporate nanotechnology, gene editing, and artificial intelligence methodologies. Furthermore, the future development trends of immunotherapy were explored in greater depth. It was posited that the convergence of artificial intelligence, multidimensional genomics, and emerging biotechnologies has presented positive prospects for the treatment of cold tumors, and has offered a theoretical foundation and technical framework for the transformation of cold tumors into \"hot tumors\".</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"9"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378254","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":"TDO2-Associated Tryptophan Metabolism Correlates with Impaired Tertiary Lymphoid Structure Maturation and Reduced B Cell Class Switching in Breast Cancer.","authors":"Weiping Yang, Wei Xiao, Wenhao Xu, Lijun Ren, Xian Li, Junhua Yu, Ronghua Wang","doi":"10.32604/or.2026.071122","DOIUrl":"10.32604/or.2026.071122","url":null,"abstract":"<p><strong>Background: </strong>Tertiary lymphoid structures (TLSs) promote antitumor immunity and predict favorable immunotherapy outcomes in breast cancer. The study aimed to investigate how Tryptophan 2,3-dioxygenase (TDO2)-associated tryptophan metabolism influences TLS maturation and B cell class switching in breast cancer.</p><p><strong>Methods: </strong>Bulk transcriptomic data from The Cancer Genome Atlas-Breast Invasive Carcinoma (TCGA-BRCA, <i>n</i> = 1055) were analyzed using Gene Set Variation Analysis (GSVA)-based metabolic scoring, immune deconvolution, and TLS quantification. Single-cell RNA sequencing (scRNA-seq, <i>n</i> = 26) and spatial transcriptomics (<i>n</i> = 1) were applied to map TDO2 expression and TLS spatial organization. Validation was performed by immunohistochemistry (<i>n</i> = 38) and multiplex immunofluorescence (<i>n</i> = 12).</p><p><strong>Results: </strong>We identified that elevated tryptophan metabolism was predominantly enriched in the Luminal A subtype and delineates an immune-cold phenotype with less immunogenicity, associated with a distinct immune-dominant cellular microenvironment, particularly enriched in T and plasma cells. High expression of the tryptophan-metabolizing enzyme TDO2 was significantly enriched in TLS-low tumors and negatively correlated with TLS maturation signatures. Functional enrichment revealed suppressed B cell class switching and attenuated C-X-C motif chemokine ligand 9 (CXCL9) expression in TLS-deficient tumors. Spatial transcriptomics and hotspot analysis demonstrated an inverse spatial correlation between TDO2 expression and TLS core components. Tumors with high tryptophan metabolism showed decreased cluster of differentiation 20 (CD20)⁺ and CXCL9⁺ cell infiltration within TLS zones. Tumors with strong TDO2-kynurenine activity displayed impaired TLS organization and attenuated humoral immunity. Conditional spatial co-occurrence modeling confirmed reduced proximity between tryptophan metabolism hotspots and TLS-related immune features.</p><p><strong>Conclusion: </strong>In conclusion, our findings suggest that TDO2-associated tryptophan metabolism is linked to impaired TLS maturation and suppressed B cell class switching in breast cancer. Targeting the TDO2-kynurenine axis may represent a promising strategy to restore TLS formation and enhance immunotherapy responsiveness in breast cancer.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"26"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378182","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":"Prognostic Significance of DNA Repair Gene mRNA Expression in Early-Stage Breast Cancer: Insights into Clinical Relevance.","authors":"Ina Shehaj, Slavomir Krajnak, Katrin Almstedt, Yaman Degirmenci, Roxana Schwab, Kathrin Stewen, Walburgis Brenner, Annette Hasenburg, Marcus Schmidt, Anne-Sophie Heimes","doi":"10.32604/or.2025.072222","DOIUrl":"10.32604/or.2025.072222","url":null,"abstract":"<p><p>The prognostic and therapeutic roles of biological markers in early-stage breast cancer (eBC) warrant further investigation. Non-Breast Cancer (BRCA) genes, along with moderate- and low-penetrance breast cancer risk variant genes, are crucial for maintaining genome stability, yet their prognostic significance in eBC remains unclear. This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients. Significant correlations were observed between the messenger ribonucleic acid (mRNA) expression levels of the genes <i>Ataxia-telangiectasia mutated (ATM), Bloom helicase gene (BLM)</i>, and <i>WRN RecQ Like Helicase (WRN)</i> and patient prognosis. High mRNA expression of ATM was associated with longer metastasis-free survival (MFS). Conversely, lower mRNA expression of BLM correlated with favorable outcomes, particularly in triple-negative tumors. Additionally, high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels. This study highlights the prognostic significance of ATM, BLM, and WRN in predicting survival outcomes in eBC patients.</p><p><strong>Background: </strong>The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer (eBC) remains unclear and warrants further investigation. This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.</p><p><strong>Methods: </strong>Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid (mRNA) expression levels. Statistical analysis, including Kaplan-Meier curves, univariable, and multivariable Cox regression analyses, was performed to assess metastasis-free survival (MFS) of mRNA expression of non-BRCA genes. Subgroup analyses were also conducted among four different molecular subtypes of eBC.</p><p><strong>Results: </strong>Our analysis revealed significant correlations between mRNA-expression levels of <i>Ataxia-telangiectasia mutated (ATM), Bloom helicase gene (BLM)</i>, and <i>WRN RecQ Like Helicase (WRN)</i> and patient prognosis. High mRNA expression of <i>ATM</i> correlated with longer MFS in the entire cohort (<i>p</i> = 0.022, Log Rank), and in luminal-B-like tumors (<i>p</i> = 0.036). Lower mRNA expression of BLM was associated with favorable outcomes (<i>p</i> = 0.011, Log Rank), particularly in triple-negative eBC (<i>p</i> = 0.030, Log Rank). Finally, high levels of <i>WRN</i> mRNA expression correlated with significantly longer MFS compared to low mRNA expression levels (<i>p</i> = 0.009, Log Rank).</p><p><strong>Conclusions: </strong>This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes, such as <i>ATM</i>, <i>BLM</i>, and <i>WRN</i>, for survival outcomes in eBC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"11"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378217","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":"Investigating the Immune Effects of Radiotherapy in Non-Small Cell Lung Cancer-Results of the PD-RAD Study.","authors":"Shuhui Cheng, Tiana Kordbacheh, Antonia Banyard, Anshuman Chaturvedi, Diego Sanchez Martinez, Crispin T Hiley, Maggie Harris, Clara Chan, Corinne Faivre-Finn, Timothy M Illidge, Eleanor J Cheadle","doi":"10.32604/or.2025.072053","DOIUrl":"10.32604/or.2025.072053","url":null,"abstract":"<p><strong>Objectives: </strong>The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer (NSCLC). However, the concurrent use of radiotherapy (RT) and durvalumab (PACIFIC-2 trial) showed no additional advantage. The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment (TME) to aid in optimizing sequencing of combination therapies.</p><p><strong>Methods: </strong>The PD-RAD trial (ClinicalTrials.gov identifier: NCT03258788) aimed to enroll thirty NSCLC patients receiving radical-intent RT. Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry (mIHC) and high-dimensional mass cytometry (CyTOF), respectively.</p><p><strong>Results: </strong>Paired biopsies were collected from only three patients (Pts 1, 3 & 4) and blood from four patients (Pts 1-4) before the study was closed early during the COVID-19 pandemic. Programmed Death-Ligand 1 (PD-L1) expression in the TME was raised in Patient 1, who responded well to treatment, and unaltered in two patients with progressive disease. CyTOF analysis revealed elevated circulating classical monocytes, highest in the patient with a good response.</p><p><strong>Conclusions: </strong>This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint. The hypothesis-generating findings highlight PD-L1⁺ macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response, but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"34 3","pages":"14"},"PeriodicalIF":4.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378251","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}