Journal of Experimental & Clinical Cancer Research最新文献

{"title":"TRP channels and cancer modulation: a voyage beyond metabolic reprogramming, oxidative stress and the advent of nanotechnologies in targeted therapy.","authors":"Marialaura Giannaccari, Chiara Florindi, Nora Bloise, Francesco Moccia, Francesco Lodola, Livia Visai","doi":"10.1186/s13046-025-03495-4","DOIUrl":"10.1186/s13046-025-03495-4","url":null,"abstract":"<p><p>Transient receptor potential (TRP) channels are a large family of non-selective cation channels that play critical roles in cellular homeostasis and signal transduction. Recent investigations have clearly highlighted their involvement in cancer biology, particularly in the regulation of cancer metabolism. Unlike normal cells, cancer cells tend to favour the energy inefficient glycolytic pathway over the more effective oxidative phosphorylation process. TRP channels are involved in critical steps of cancer-related metabolic reprogramming by influencing intracellular Ca²⁺ signaling. Their dysregulation can intensify oxidative stress, thereby promoting oncogenic transformation and tumor progression. The intricate interplay between TRP channels, metabolic reprogramming and oxidative stress promotes cancer cell progression and resistance to treatment. This review highlights the crucial role of TRP channels in tumorigenesis. It examines how TRPM7 and TRPM8 contribute to metabolic reprogramming by its involvement in glycolysis pathway. Additionally, it explores the involvement of TRPML1, TRPA1, TRPM2, and TRPV1 in modulating reactive oxygen species (ROS) levels within cancer cells, analyzing the ROS dual role in tumor modulation. The advent of nanotechnology, particularly through the utilisation of engineered nanoparticles, has facilitated the selective modulation of TRPA1, TRPM2, and TRPV1 channels. This technological breakthrough has paved the way for novel and more targeted anticancer treatment strategies. The integration of molecular insights with cutting-edge technological approaches holds great promise for the development of more effective and targeted cancer treatments.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"240"},"PeriodicalIF":12.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tfcp2l1 as a central integrator of hypoxia, dedifferentiation, and tumor progression.","authors":"Cynthia Clemente-González, Amancio Carnero","doi":"10.1186/s13046-025-03501-9","DOIUrl":"10.1186/s13046-025-03501-9","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"236"},"PeriodicalIF":12.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.","authors":"Kimberley M Hanssen, Jayne Murray, Ruby Pandher, Stephanie Alfred, Laura D Gamble, Jennifer Brand, Erin Mosmann, Frances K Kusuma, Crystal Mak, Adam Kearns, Alvin Kamili, Caroline Atkinson, Alexis Z Minchaca, Jean Bertoldo, David S Ziegler, Francis Mussai, Paul N M Cheng, Murray D Norris, Jamie I Fletcher, Michelle Haber","doi":"10.1186/s13046-025-03502-8","DOIUrl":"10.1186/s13046-025-03502-8","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated amino acid metabolism creates cancer-specific vulnerabilities. Neuroblastoma tumors have dysregulated arginine metabolism that renders them sensitive to systemic arginine deprivation. Arginase therapy has been proposed as a therapeutic approach for neuroblastoma treatment and has a favorable safety profile in pediatric cancer patients, however optimal therapeutic combinations remain unexplored.</p><p><strong>Methods: </strong>The anti-tumor effects of BCT-100, a pegylated human arginase, were studied in neuroblastoma cell models by metabolite profiling, proteomics, and viability, clonogenicity, and protein translation assays. BCT-100 efficacy was assessed in the Th-MYCN transgenic neuroblastoma mouse model and in neuroblastoma cell line and patient-derived xenograft models.</p><p><strong>Results: </strong>In vitro, depletion of arginine by BCT-100 arrested protein translation and cellular proliferation, with effects on clonogenicity enhanced in combination with standard-of-care chemotherapeutics SN-38/temozolomide and mafosfamide/topotecan. In vivo, BCT-100 treatment spared liver arginine while significantly depleting plasma and tumor arginine in Th-MYCN mice, and extended tumor latency (> 100 vs. 45.5 days) in mice pre-emptively treated at weaning. In mice with established tumors, BCT-100 prolonged tumor progression delay when combined with standard-of-care chemo- (> 90 vs. 25 days) or chemo-immuno-therapy (49.5 vs. 35.5 days). Tumor progression delay was also observed in cell line and patient-derived xenografts with BCT-100 treatment, including relapsed/refractory disease models. No increased toxicity was observed with the addition of BCT-100 to established therapies.</p><p><strong>Conclusions: </strong>The arginase BCT-100 profoundly disrupts neuroblastoma growth in vitro and in vivo, an effect enhanced in combination with standard-of-care chemo-immuno-therapy. Our data supports further assessment of arginine-depleting combination therapies as a new treatment strategy for neuroblastoma.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"239"},"PeriodicalIF":12.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HAS1^high cancer associated fibroblasts located at the tumor invasion front zone promote oral squamous cell carcinoma invasion via ECM remodeling.","authors":"Wanyong Jin, Qiuya Yu, Liyuan Yu, Ting Zhou, Xiren Wang, Wanqiu Lu, Xiaoxin Zhang, Liang Ding, Qingang Hu, Yanhong Ni","doi":"10.1186/s13046-025-03493-6","DOIUrl":"10.1186/s13046-025-03493-6","url":null,"abstract":"<p><strong>Background: </strong>Although tumor cell heterogeneity between the tumor center (TC) and invasion front (IF) of oral squamous cell carcinoma (OSCC) is well documented, the morphological, molecular, and functional characteristics of cancer-associated fibroblasts (CAFs) in these regions remain poorly understood.</p><p><strong>Methods: </strong>We examined hematoxylin and eosin (H&E)-stained OSCC sections to assess CAF morphology and correlation with patient prognosis. We then isolated paired CAFs from the tumor center (CAF^TC) and invasion front (CAF^IF) of four OSCC patients and compared their ECM-remodeling activity and pro-tumorigenic effects on OSCC cells. Furthermore, RNA sequencing identified differentially expressed genes between CAF^TC and CAF^IF. Finally, based on RNA-seq findings, we knocked down hyaluronan synthase 1 (HAS1) in CAF^IF to evaluate its role in extracellular matrix (ECM) remodeling and tumor invasion.</p><p><strong>Results: </strong>Compared to CAF^TC, CAF^IF exhibited a plump cell morphology and were associated with shorter disease-free survival. Functionally, CAF^IF showed higher ECM-remodeling activity and more effective ability for promoting OSCC invasion and lymph node metastasis than CAF^TC. RNA-seq identified HAS1 was significantly upregulated in CAF^IF, promoting hyaluronic acid (HA) production and ECM remodeling. HAS1 knockdown in CAF^IF diminished ECM remodeling and attenuated the ability of CAF^IF to promoting OSCC invasion.</p><p><strong>Conclusion: </strong>CAF^IF with plump cell morphology showed pro-invasive abilities, driven in part by HAS1 overexpression and ECM remodeling, suggesting that targeting HAS1-driven ECM remodeling could be a promising therapeutic strategy.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"238"},"PeriodicalIF":12.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC).","authors":"Weijun Hong, Min Xue, Jun Jiang, Yajuan Zhang, Xiwen Gao","doi":"10.1186/s13046-025-03499-0","DOIUrl":"10.1186/s13046-025-03499-0","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"235"},"PeriodicalIF":12.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone lactylation-boosted AURKB facilitates colorectal cancer progression by inhibiting HNRNPM-mediated PSAT1 mRNA degradation.","authors":"Yuyi Li, Jinjin Peng, Di Wu, Qingxin Xie, Yichao Hou, Linjing Li, Xintian Zhang, Yu Liang, Jing Feng, Jiaqing Chen, Wangshuang Chen, Che Xu, Han Yao, Xiangjun Meng","doi":"10.1186/s13046-025-03498-1","DOIUrl":"10.1186/s13046-025-03498-1","url":null,"abstract":"<p><strong>Background: </strong>Aurora kinase B (AURKB), a key regulator of mitosis, is frequently upregulated in various malignancies, including colorectal cancer (CRC), and is associated with poor prognosis. However, the limited clinical efficacy of AURKB inhibitors suggests the existence of previously unrecognized oncogenic mechanisms that merit further investigation.</p><p><strong>Methods: </strong>AURKB was prioritized through bioinformatic analysis, and its elevated expression in CRC was validated via single-cell RNA sequencing (scRNA-seq) and western blot. The transcriptional activation of AURKB was attributed to H3K18 lactylation, as confirmed by chromatin immunoprecipitation (ChIP)-qPCR. RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA) were conducted to pinpoint the downstream targets of AURKB. The role of the AURKB/phosphoserine aminotransferase 1 (PSAT1) axis in CRC was further studied using both in vitro and in vivo functional experiments. Mass spectrometry, co-immunoprecipitation (Co-IP), proximity ligation assay (PLA), RNA immunoprecipitation (RIP)-qPCR, and mRNA stability assays were employed to investigate the interplay and potential mechanisms involving AURKB, heterogeneous nuclear ribonucleoprotein M (HNRNPM), and PSAT1.</p><p><strong>Results: </strong>AURKB was identified as an oncogene linked to advanced pathological staging and poor clinical outcomes in CRC. Its transcriptional upregulation was driven by H3K18 lactylation at its promoter. PSAT1 was further identified as a key downstream effector in AURKB-mediated CRC progression. Mechanistically, AURKB bound to HNRNPM and interfered with its interaction with PSAT1 mRNA, thereby suppressing HNRNPM-mediated mRNA degradation and ultimately increasing PSAT1 protein levels.</p><p><strong>Conclusion: </strong>Our findings uncover a previously unappreciated, kinase-independent function of AURKB in CRC, redefining its therapeutic relevance beyond kinase inhibition. This highlights the need for broader targeting strategies, including PROTAC-mediated degradation of AURKB and pharmacological inhibition of the AURKB/PSAT1 axis, to fully harness its role in CRC treatment.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"233"},"PeriodicalIF":12.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.","authors":"Manon Desgres, Melis Poyraz, Buse Sari, François P Duhoux, Cédric van Marcke, Cyril Corbet","doi":"10.1186/s13046-025-03500-w","DOIUrl":"10.1186/s13046-025-03500-w","url":null,"abstract":"<p><p>Neoadjuvant chemotherapy (NAC) is a cornerstone in the treatment of early-stage high-risk breast cancers (BC), particularly in triple-negative, HER2-positive, and selected hormone receptor-positive subtypes. However, its effectiveness is frequently hindered by intrinsic or acquired resistance, resulting in a significant residual cancer burden (RCB) in more than half of patients. Despite extensive genomic profiling, reliable predictive biomarkers for treatment response remain limited, impeding the development of personalized therapeutic strategies. Emerging evidence highlights tumor metabolic reprogramming as a key non-genetic mechanism contributing to NAC resistance. In this review, we critically examine current advances in metabolic imaging and metabolomics as tools to predict NAC response in BC. We also discuss the role of the tumor microenvironment (TME), including hypoxia and acidosis, in shaping metabolic plasticity and fostering treatment resistance. Furthermore, we explore novel therapeutic strategies targeting metabolic pathways, ranging from enzyme inhibition to dietary interventions, and the use of advanced preclinical models. Together, these insights offer a metabolic framework for overcoming NAC resistance and advancing precision oncology in early-stage BC.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"234"},"PeriodicalIF":12.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting NOTCH1-KEAP1 axis retards chronic liver injury and liver cancer progression via regulating stabilization of NRF2.","authors":"Chunxiao Chang, Meng Wang, Jia Li, Sihao Qi, Xiaojuan Yu, Jun Xu, Shengbin Shi","doi":"10.1186/s13046-025-03488-3","DOIUrl":"10.1186/s13046-025-03488-3","url":null,"abstract":"<p><strong>Background: </strong>Chronic liver injury is a key factor in diseases like hepatocellular carcinoma (HCC), steatohepatitis (NASH), and viral hepatitis type B and C (HBV, HCV). Understanding its molecular mechanisms is crucial for effective treatment. The NOTCH1 signaling pathway, though not fully understood, is implicated in liver injury and may be a potential therapeutic target.</p><p><strong>Methods: </strong>Clinical HCC, HBV, HCV and NASH samples and additional in vitro and in vivo performances were subjected to confirm the role of NOTCH1 and its downstream targets via a series of biochemical assays, molecular analysis approaches and targeted signaling pathway assay, etc. RESULTS: The present study first verified the abnormal elevation of NOTCH1 in hepatocytes from patients with steatohepatitis, HCC, HBV, HCV, and mouse models. Crucially, we discovered that hepatocyte-specific NOTCH1 knockout reduces hepatocellular damage in chronic liver inflammation and HCC mouse models, whereas adeno-associated virus serotype 8 (AAV8)-mediated NOTCH1 overexpression in hepatocytes exacerbates liver injury-related phenotype on-setting. Mechanistically, we showed that NOTCH1 has a new role in controlling ferroptosis and oxidative damage in hepatocytes. It interacts with Kelch-like ECH-associated protein 1 (KEAP1) and is directly recruited through its intracellular domain (NICD1). Additionally, the KEAP1 recruited by NOTCH1 impeded the binding stability of KEAP1-NFE2 like BZIP transcription factor 2 (Nrf2), promote the separation of KEAP1 and Nrf2, thereby reducing the stability of Nrf2 and hindering the ubiquitination-related proteasome degradation of Nrf2. Crucially, we also discovered that NOTCH1's ANK domain is essential for NICD1-KEAP1 contacts and signaling activation. The inability of NOTCH1 with ANK domain mutants (ΔANK) to connect with KEAP1 and increase its expression emphasizes the importance of the ANK domain in KEAP1-NRF2 signaling. By reversing the downregulation of KEAP1 and the overexpression of NRF2, ANK function is linked to ferroptosis and ROS buildup. ANK domain targeting may slow the course of HCC and liver damage.</p><p><strong>Conclusions: </strong>Targeting the NOTCH1-KEAP1-NRF2 axis as a possible chronic hepatic injury therapy is supported by these findings, which identify NOTCH1-KEAP1 as an NRF2 suppressor that accelerates the progression of liver injury.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"232"},"PeriodicalIF":12.8,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCT196969 inhibits TNBC by targeting the HDAC5/RXRA/ASNS axis to down-regulate asparagine synthesis.","authors":"Qiong Yuan, Qi Wang, Jun Li, Liyang Yin, Shu Liu, Xuyu Zu, Yingying Shen","doi":"10.1186/s13046-025-03494-5","DOIUrl":"10.1186/s13046-025-03494-5","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) seriously threatens the health of patients, and new therapeutic targets and drugs need to be explored. Studies have shown that CCT196969 can inhibit melanoma and colorectal cancer. However, the role of CCT196969 in TNBC is unclear.</p><p><strong>Methods: </strong>CCT196969 inhibited TNBC via in vitro and in vivo experiments. Transcriptomic analysis, metabolomics analysis, proteomic analysis, and other experiments were used to determine that CCT196969 inhibited asparagine synthetase (ASNS) expression and downstream mTOR signaling pathway, and that Retinoid X Receptor Alpha (RXRA) was the upstream transcription factor that regulated ASNS. The binding sites of RXRA and ASNS promoter were determined by luciferase and Chromatin Immunoprecipitation (CHIP) assay. Histone Deacetylase 5 (HDAC5) was confirmed as the key target of CCT196969 by target capture assay, Cell thermal shift assay (CETSA), Surface plasmon resonance (SPR) and other experiments. qPCR, CHX tracer, MG132, immunofluorescence (IF) and Co-Immunoprecipitation (CO-IP) assay were used to detect the regulation of HDAC5 on RXRA transcription and post-translation level, and the key domains of interaction and binding between HDAC5 and RXRA. The binding sites of HDAC5 and RXRA were predicted by PyMOL software. The effect of HDAC5 on the acetylation and ubiquitination levels of RXRA was examined by CO-IP experiment. The deacetylation site of HDAC5 to RXRA was investigated by IP experiments and mass spectrometry.</p><p><strong>Results: </strong>This study reveals that CCT196969 can inhibit TNBC by down-regulating the expression of ASNS, inhibiting asparagine synthesis and downstream mTORC pathway. Mechanistically, CCT196969 targeted and inhibited HDAC5, reducing the interaction of its 1-291 region with RXRA's 1-98 region, and further resulting in an increase in RXRA acetylation (K410 and K412) and a decrease in ubiquitination levels. Together, these effects up-regulated the transcriptional and post-translational levels of RXRA. Finally, RXRA inhibited the expression of ASNS at the transcriptional level by binding to the - 1114/-1104 region on the ASNS promoter as a transcription suppressor.</p><p><strong>Conclusions: </strong>This study reveals a previously unrecognized anti-TNBC mechanism of CCT196969 through the HDAC5/RXRA/ASNS axis. This provides potential candidate targets for the treatment of TNBC and a theoretical basis for the clinical treatment of TNBC patients with CCT196969.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"231"},"PeriodicalIF":12.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioblastoma metabolomics: uncovering biomarkers for diagnosis, prognosis and targeted therapy.","authors":"Susan Costantini, Elena Di Gennaro, Giulia Fanelli, Palmina Bagnara, Chiara Argenziano, Carmen Maccanico, Marco G Paggi, Alfredo Budillon, Claudia Abbruzzese","doi":"10.1186/s13046-025-03497-2","DOIUrl":"10.1186/s13046-025-03497-2","url":null,"abstract":"<p><p>Glioblastoma (GBM) is characterized by rapid growth, high molecular heterogeneity, and invasiveness. Specific aggressive factors are represented by MGMT promoter methylation, and IDH mutation status. Current standard-of-care for GBM includes surgical resection, followed by radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide. However, patients almost invariably succumb due to therapy resistance and disease recurrences. Therefore, novel therapies for GBM are urgently needed to improve patient survival, necessitating the identification of new diagnostic and prognostic biomarkers, as well as therapeutic targets.In this context, \"omics\" technologies, such as metabolomics and lipidomics, can generate vast amounts of data useful to elucidate the complex molecular mechanisms driving this disease, and discover potential novel biomarkers and therapeutic targets. Our review aims to highlight the current literature on the metabolomics studies conducted on GBM biological matrices, such as in vitro and in vivo models, tissues and biofluids, including plasma, saliva and cerebrospinal fluid.From the data reported here, it appears that metabolic reprogramming in GBM is characterized by dysregulation in multiple pathways, particularly glycolysis (Warburg effect), amino acid metabolism, and the urea cycle, and the metabolic changes disclose promising tumor targets.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"230"},"PeriodicalIF":12.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}