Discover. Oncology最新文献

{"title":"D-mannose suppresses HIF-1α mediated metabolic reprogramming in clear cell renal cell carcinoma.","authors":"Ziyin Tian, Ruonan Zhang, Yan Ma, Jiaxi Li, Yunliang Li, Lei Lv","doi":"10.1007/s12672-025-03695-6","DOIUrl":"10.1007/s12672-025-03695-6","url":null,"abstract":"<p><p>The inactivation mutation of VHL drives the progression of clear cell renal cell carcinoma (ccRCC), while the deletion of VHL leads to the failure of HIF-1/2α to degrade normally through the ubiquitin proteasome pathway. Notably, the abnormal accumulation of HIF-1/2α results in metabolic reprogramming and promotes the occurrence of tumors. Therefore, inhibition of metabolic reprogramming of ccRCC may be an effective treatment. In methodology, the viabilities of tumor cells were detected by cell counting kit-8 assay in vitro. The expression levels of related proteins were analyzed by western blotting assay, and the mRNA levels of genes were assessed by RT-qPCR assay. Glucose uptake, intracellular lactate and NADPH production were measured according to relevant instructions. Here, we found that D-mannose inhibits the proliferation of ccRCC in vitro. Mechanistically, D-mannose suppresses the transcription of HIF-1α downstream target genes, including GLUT1, LDHA, PDK1 and VEGF, by downregulating the protein level of HIF-1α in ccRCC cells. Furthermore, D-mannose reduces glucose uptake and intracellular lactate and NADPH production. To sum up, this study demonstrates that targeting HIF-1α by D-mannose to inhibit metabolic reprogramming is a promising strategy for ccRCC and complements a previously unknown role of D-mannose in cancer treatment.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1934"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336378","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":"From cold to hot tumors: feasibility of applying therapeutic insights to TNBC.","authors":"Shaozhang Yan, Xinyue Sun, Kuanyu Wang","doi":"10.1007/s12672-025-03745-z","DOIUrl":"10.1007/s12672-025-03745-z","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is characterized by the absence of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). Due to its immunosuppressive tumour microenvironment (TME) and low immune cell infiltration, TNBC typically exhibits poor responsiveness to immunotherapy. Recent relevant research has focused on using strategies to convert cold tumors into hot tumors to increase tumor immunogenicity and improve treatment efficacy. This review aims to summarize the biological characteristics of both cold and hot tumors and explore the mechanisms underlying the transformation from cold to hot tumors. Key strategies include modulation of the TME, enhancement of immune cell infiltration, and regulation of the inflammatory responses. Additionally, the roles of immune checkpoint inhibitors (ICIs), cytokine therapy, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines in reprogramming the TME are discussed. Further, the emerging combination strategies, such as the integration of ICIs with chemotherapy, radiotherapy, and targeted therapies, have been evaluated for their potential to increase TNBC immunogenicity. Current preclinical and clinical evidence suggests that reprogramming the TME through targeted interventions significantly increases immune cell infiltration and antigen presentation, thereby improving the immunotherapy efficacy in TNBC. The combinations of ICIs with chemotherapy and radiotherapy have shown promise in shifting the TME toward an immunoresponsive state. Moreover, advances in the CAR-T-cell therapy, cytokine therapy, and cancer vaccines have offered novel approaches for overcoming immune resistance in TNBC. In conclusion, transforming cold tumors into hot tumors represents a promising therapeutic strategy for TNBC. Future research should focus on optimizing the treatment combinations, refining therapeutic timing and dosage, and integrating precision medicine approaches to achieve maximized clinical benefits. A deeper understanding of TME modulation and immune resistance mechanisms would facilitate the development of novel immunotherapeutic strategies to improve the survival outcomes and quality of life in TNBC patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1942"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336502","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":"TAM family kinases are potential candidate targets for therapeutic intervention in chronic myeloid leukemia.","authors":"Maryam Yousaf, Khadija Arif, Dilawar Khan","doi":"10.1007/s12672-025-03632-7","DOIUrl":"10.1007/s12672-025-03632-7","url":null,"abstract":"<p><strong>Background: </strong>Chronic Myeloid Leukemia (CML) is a hematologic disorder depicted by BCR::ABL1 translocation; a constitutively active tyrosine kinase (TK) and a hallmark of CML. Kinase domain mutations and the activation of alternative signaling pathways lead to drug resistance in CML. TAM family kinases, including TYRO3 receptor tyrosine kinase (TYRO3-RTK), AXL receptor tyrosine kinase (AXL-RTK), and MER receptor tyrosine kinase (MERTK), are often overexpressed in various types of cancers. AXL-RTK plays a significant role in the survival of leukemic stem cells (LSCs) and provides adaptive resistance to CML cells against Tyrosine kinase inhibitors (TKIs). However, the specific functions and mechanisms of two other receptors, TYRO3-RTK and MERTK, in both sensitive and resistant CML cells are not yet documented. Therefore, this study aimed to explore the expression patterns and roles of TAM family kinases in sensitive and resistant CML.</p><p><strong>Methods and results: </strong>We have developed an Imatinib-Resistant CML model (K562-R) by administering an increasing dose of Imatinib over 4 months. Proliferation was evaluated through MTT assay. Apoptosis and expression analysis were conducted through the DNA fragmentation assay and RT-PCR, respectively. TYRO3-RTK, AXL-RTK, and MERTK were found to be 2, 7 and 25 folds higher in K562-R than K562-S cells respectively. Pharmacological targeting of TYRO3-RTK with LDC1267, AXL-RTK with R428, and MERTK with UNC2250 TAM inhibitors significantly interfered with the proliferation potential of both K562-S and K562-R cells. TAM kinase inhibitors also abridged colony formation in K562-S and K562-R cells. We have observed an additive antiproliferation effect by co-targeting TAM kinases with Imatinib in K562-S cells and a synergistic effect in K562-R cells. Mechanistically, apoptosis induction independent of p53, differential upregulation of cell cycle inhibitors, including p16, p21, and p27 in K562-S and K562-R cells were observed to be related with the proliferation inhibition. Furthermore, we showed that TAM family inhibitors interfere with the Wnt/β-catenin pathway by downregulation of downstream targets c-Myc, Axin2, its regulators, EYA3, and AXL-RTK in both K562-S and K562-R cells.</p><p><strong>Conclusion: </strong>TAM family kinase inhibitors significantly reduce the proliferation and colony formation of K562-S and K562-R cells by inducing apoptosis, interfering with Wnt/β catenin pathway, and upregulating cell cycle inhibitors.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1944"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336593","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":"Association of antipsychotic drug target genes and risk of lung cancer: a Mendelian randomization study.","authors":"Jun Xiang, Guangming Xiang, Ming Zhan, Lingyun Zhang, Huaqian Zeng, Xinyu Song","doi":"10.1007/s12672-025-03659-w","DOIUrl":"10.1007/s12672-025-03659-w","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotic drugs are associated with various tumors, but their causal relationship with lung cancer risk remains unclear. We aimed to investigate this association using Mendelian randomization (MR) analyses.</p><p><strong>Methods: </strong>We performed summary-data-based MR (SMR) using blood-derived expression quantitative trait loci (eQTL) and two sample-MR using single nucleotide polymorphism (SNP) of antipsychotic drug target genes. Colocalization analysis was performed with cis-eQTLs, and sensitivity analyses included the Heterogeneity in dependent instruments (HEIDI) test and Multi-SNP-based SMR.</p><p><strong>Results: </strong>SMR showed that higher DRD4 expression was associated with lower lung cancer risk (P_SMR = 0.009; P_HEIDI >0.01; P_SMR_multi = 0.0338). Two-sample MR further indicated inverse associations for KCNH2 (OR: 0.91; 95%CI: 0.83-0.99; P = 0.040) and DRD4 (OR: 0.89; 95%CI: 0.79-0.99; P = 0.040) with lung cancer risk. Additionally, elevated HTR6 and DRD4 expression was linked to decreased lung adenocarcinoma (LUAD) risk (HTR6, OR: 0.89; 95%CI: 0.81-0.99; P = 0.014; DRD4, OR: 0.87; 95%CI: 0.76-0.98; P = 0.016). Colocalization analyses did not support shared causal variants (PP.H4 < 0.8).</p><p><strong>Conclusion: </strong>These findings provide insights into the potential oncologic implications of antipsychotic drug use and may inform clinical management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1925"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336442","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":"Expressions, immune associations, and prognostic values of mitochondrial ribosomal protein MRPL3 in the pan cancer landscape.","authors":"Jing Lin, Wenzhe Chen, Yaodong Zhao, GuanZhong Qiu","doi":"10.1007/s12672-025-03770-y","DOIUrl":"10.1007/s12672-025-03770-y","url":null,"abstract":"<p><strong>Background: </strong>MRPL3, a member of the mitochondrial ribosomal family, is involved in the translation of mitochondria-related proteins. However, its role in tumors remains unclear.</p><p><strong>Objective: </strong>To elucidate the oncogenic role and prognostic significance of MRPL3 in cancer.</p><p><strong>Methods: </strong>We conducted a pan-cancer analysis of MRPL3 using various databases, bioinformatics and statistical tools, as well as tissue microarray analysis.</p><p><strong>Results: </strong>MRPL3 was generally upregulated in tumors compared to normal tissues. Its expression showed a negative correlation with immunogenic markers, immune cell infiltration, and immune checkpoint genes (ICGs) in most cancers, suggesting an immunosuppressive role in the tumor microenvironment (TME). Genes interacting with and similar to MRPL3 were involved in key signaling pathways across cancers. MRPL3 overexpression was frequently associated with poor prognosis and identified as an independent prognostic risk factor in KIRC, LUSC, LIHC, MESO, UCEC, and PAAD.</p><p><strong>Conclusion: </strong>MRPL3 is overexpressed in multiple cancers and plays an immunosuppressive role, significantly correlating with poor prognosis, indicating its potential as a therapeutic target in cancer treatment.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1928"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336486","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":"COL22A1 expression identifies aggressive glioma and independently predicts survival through integrated multiomics and clinical validation.","authors":"Wei-Wen Hsu, Wen-Shin Song, Pei-Chi Chang, Dueng-Yuan Hueng, Yao-Feng Li","doi":"10.1007/s12672-025-03723-5","DOIUrl":"10.1007/s12672-025-03723-5","url":null,"abstract":"<p><strong>Background: </strong>Gliomas, especially IDH‑wildtype astrocytomas, remain lethal despite multimodal therapy. Collagen type XXII alpha-1 (COL22A1) exhibits oncogenic activity in other cancers but remains underexplored in brain tumors. We asked whether its expression, cellular origin, and spatial context add prognostic and translational value in diffuse glioma.</p><p><strong>Methods: </strong>We reprocessed TCGA/CGGA RNA‑seq to transcripts‑per‑million and re‑annotated tumours under the WHO 2021 taxonomy. Differential expression, Kaplan-Meier, and multivariable Cox models assessed survival associations; gene‑set enrichment profiled pathway context. Cell‑type sources were mapped by deconvolution and single‑cell datasets (GSE131928, GSE89567), and spatial distribution was examined using Ivy GAP and 10 × Visium. Protein abundance was validated by quantitative immunohistochemistry in 75 surgical specimens, with orthogonal proteomic corroboration from the TCGA Proteomic Data Commons.</p><p><strong>Results: </strong>COL22A1 mRNA was up‑regulated in glioma and increased with grade. High expression predicted shorter overall survival and remained an independent hazard factor after adjusting for age, grade, Karnofsky score, radiotherapy, and temozolomide. Transcriptome deconvolution and Single‑cell analyses localized COL22A1 predominantly to mesenchymal-like tumour subpopulations with negligible signal in lymphoid, reactive-glial, or myeloid compartments. Spatial transcriptomics showed marked enrichment in peri‑necrotic and microvascular proliferation niches. Gene Set Enrichment Analysis (GSEA) linked COL22A1‑high tumours to epithelial-mesenchymal transition, cell-cycle, and inflammatory (IL6/JAK-STAT3, TNF-NFκB) programmes, consistent with a proliferative and hypoxic phenotype. Immunohistochemistry confirmed higher protein abundance in tumours versus normal brain, a stepwise increase with grade, and a trend association with Ki‑67; mass‑spectrometry data corroborated increased protein abundance and adverse survival at high expression. A parsimonious nomogram combining COL22A1 with clinical covariates improved the prediction of 1-, 3-, and 5-year survival.</p><p><strong>Conclusions: </strong>Across bulk, single‑cell, and spatial layers, COL22A1 integrates molecular, cellular, and microenvironmental hallmarks of glioma aggressiveness. Its tumour‑centric expression, peri‑necrotic localisation, and independent prognostic value support COL22A1 as a robust biomarker and a tractable candidate for imaging or therapeutic strategies in treatment‑refractory disease.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1945"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336364","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":"Potential causal association and mechanistic insights of chronic HBV infection in extrahepatic cancer progression.","authors":"Zhihui Wei, Weiqiang Wu","doi":"10.1007/s12672-025-03724-4","DOIUrl":"10.1007/s12672-025-03724-4","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis B virus (HBV) infection is a major global health concern, contributing to both hepatic and extrahepatic complications, including cancer. While its association with liver cancer is well established, the role of HBV in extrahepatic malignancies remains less clear. This study aimed to investigate the potential causal relationship between chronic HBV infection and common extrahepatic cancers.</p><p><strong>Methods: </strong>We applied Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data to assess causal links between chronic HBV infection and extrahepatic cancer risk. Transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes (DEGs) and explore potential mechanisms.</p><p><strong>Results: </strong>MR analysis revealed a significant causal association between chronic HBV infection and increased risks of breast and lung cancers. Key DEGs, including SPP1 and PDK4, were identified, implicating molecular pathways involved in tumor progression.</p><p><strong>Conclusion: </strong>Our findings indicate a modest but significant link between chronic HBV infection and elevated extrahepatic cancer risk, highlighting potential therapeutic targets for HBV-infected individuals. These results support the need for personalized monitoring and treatment strategies in precision oncology.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1939"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336487","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":"The oncogenic role of miR-155 on oral cancer progression and treatment strategies.","authors":"Alexandra Iulia Aghiorghiesei, Nikolay Mehterov, Andreea Nutu, Boyan Vladimirov, Boyan Nonchev, Christos K Kontos, Rares Buduru, Cornelia Braicu, Ioana Berindan-Neagoe","doi":"10.1007/s12672-025-03467-2","DOIUrl":"10.1007/s12672-025-03467-2","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy within head and neck cancers, often associated with risk factors such as tobacco use, alcohol consumption, and HPV infection. MicroRNAs (miRNAs), small non-coding RNAs that inhibit target genes, are a promising new focus as biomarkers or therapeutic targets for cancer treatment. miR-155 has emerged as a significant regulator in various cancers, including OSCC, where its altered expression is linked to tumor initiation, progression, and resistance to treatment. miR-155 is a well-studied miRNA that has an oncogenic role in several solid tumors, including oral cancer. Studies suggest that miR-155 modulates key cellular processes such as proliferation, apoptosis, and immune response, making it a promising biomarker and potential therapeutic target. Investigating the mechanisms through which miR-155 drives OSCC progression could pave the way for enhanced diagnostic and therapeutic approaches, addressing essential needs in managing this aggressive cancer type. The present paper highlights the oncogenic role of miR-155 in oral cancers, summarizing recent advancements in therapeutically targeting this transcript, including preclinical testing of miR-155 inhibitors. This approach offers a promising new avenue for treating drug-resistant oral cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1941"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336628","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":"EGFR gene amplification in IDH-wildtype glioblastomas: an integrative bioinformatic and histopathological analysis using immunohistochemistry and fluorescence in situ hybridization.","authors":"Anass Oukhdouch, Basma Zinbi, Souad Sellami, Hanane Rais","doi":"10.1007/s12672-025-03390-6","DOIUrl":"10.1007/s12672-025-03390-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults, characterized by marked histopathological features such as high proliferative activity, mitoses, necrosis, and microvascular proliferation (MVP), as well as extensive molecular heterogeneity. Among key molecular alterations, EGFR amplification and MGMT promoter methylation hold significant diagnostic and prognostic relevance. In this study, we performed a comprehensive bioinformatic analysis of EGFR and conducted a correlation analysis of EGFR amplification in a cohort of 19 GBM samples using standard fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). These results were further correlated with established molecular hallmarks of glioblastoma.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analyzed mRNA expression profiles of EGFR family genes using publicly available datasets from the Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) databases. Additionally, we utilized multiple online bioinformatics platforms, including GEPIA, TIMER, TISIDB repository, cBioPortal, Metascape, and GeneMANIA, to explore the expression patterns, immune cell infiltration, correlation of EGFR amplification with immunomodulatory and prognostic significance of the EGFR family in glioblastoma. EGFR amplification and protein expression were assessed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. MGMT promoter methylation was determined by methylation-specific qPCR (MS-qPCR).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Bioinformatic analyses revealed that EGFR and ERBB2 were overexpressed and associated with poor prognosis, while ERBB3 and ERBB4 exhibited decreased expression in GBM compared to normal brain tissue. Immune infiltrating level correlation of EGFR family, revealed that EGFR and ERBB4 expression were positively correlated with various immune cell infiltrates in glioblastoma, particularly CD8 + T cells, macrophages, and B cells. Additionally, EGFR expression was negatively correlated with key co-stimulatory molecules including CD28, CD40, CD70, and IL2RA, no significant associations were found with classical immune checkpoints such as PD-L1 and CTLA-4, though EGFR was inversely correlated with TGFBR1. Subtype analysis showed elevated EGFR expression in Classical-like and Mesenchymal-like GBM subtypes, and a trend toward higher levels in the lymphocyte-depleted immune subtype. Genomic analysis revealed that EGFR family alterations in 49% of GBM cases, with EGFR amplification being the most frequent and linked to poorer overall survival. Enrichment and the PPI network analyses demonstrated that the EGFR family is deeply involved in tumorigenic pathways, particularly PI3K/AKT signaling, integrin interactions, and growth factor receptor cascades. We found that EGFR amplification was detected in 36.84% of cases and was significantly associated with EGFR protein overexpression (IHC score 3+)","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1931"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336387","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":"Emerging photothermal agents combined with immunotherapy for cancer treatment.","authors":"Tian Xu, Xueping Yang, Xinyu Chen, Qilin Wang, Juncai Ye, Chuanyu You, Jiao Zhu, Yan Gui","doi":"10.1007/s12672-025-03669-8","DOIUrl":"10.1007/s12672-025-03669-8","url":null,"abstract":"<p><strong>Background: </strong>Immunophotothermal therapy (IPTT), combining immune checkpoint inhibitors and photothermal therapy, represents a promising synergistic anticancer strategy that enhances tumour-specific immunity alongside localised thermal ablation.</p><p><strong>Aim: </strong>This review aims to summarise and critically analyse recent advancements in the development of photothermal agents for IPTT and their synergistic applications with immune checkpoint inhibitors.</p><p><strong>Methods: </strong>We focus specifically on the progress in innovative photothermal agent materials, the underlying mechanisms of immunophotothermal synergy, and the resulting antitumor efficacy evidenced by preclinical and clinical findings.</p><p><strong>Conclusions: </strong>Furthermore, the key challenges hindering clinical translation and potential future directions are discussed. This comprehensive analysis highlights the current state and prospects of IPTT as an effective multimodal cancer treatment paradigm.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1936"},"PeriodicalIF":2.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336455","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}