Open Access
Review
| Issue |
Vis Cancer Med
Volume 6, 2025
|
|
|---|---|---|
| Article Number | 15 | |
| Number of page(s) | 10 | |
| DOI | https://doi.org/10.1051/vcm/2025015 | |
| Published online | 09 January 2026 | |
- PatelAP, TiroshI, TrombettaJJ, ShalekAK, GillespieSM, WakimotoH, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344:1396–1401. 10.1126/science.1254257 [Google Scholar]
- NeftelC, LaffyJ, FilbinMG, HaraT, ShoreME, RahmeGJ, et al. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell. 2019;178:835–849 e821. 10.1016/j.cell.2019.06.024 [Google Scholar]
- TiroshI, SuvaML. Cancer cell states: Lessons from ten years of single-cell RNA-sequencing of human tumors. Cancer Cell. 2024; 42:1497–1506. 10.1016/j.ccell.2024.08.005 [Google Scholar]
- WangX, SunQ, LiuT, LuH, LinX, WangW, et al. Single-cell multi-omics sequencing uncovers region-specific plasticity of glioblastoma for complementary therapeutic targeting. Sci Adv. 2024;10:eadn4306. 10.1126/sciadv.adn4306 [Google Scholar]
- GreenwaldAC, DarnellNG, HoefflinR, SimkinD, MountCW, Gonzalez CastroLN, et al. Integrative spatial analysis reveals a multi-layered organization of glioblastoma. Cell. 2024;187:2485–2501 e2426. 10.1016/j.cell.2024.03.029 [Google Scholar]
- VerhaakRG, HoadleyKA, PurdomE, WangV, QiY, WilkersonMD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98–110. 10.1016/j.ccr.2009.12.020 [Google Scholar]
- WangQ, HuB, HuX, KimH, SquatritoM, ScarpaceL, et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell. 2017;32:42–56 e46. 10.1016/j.ccell.2017.06.003 [Google Scholar]
- TiroshI, IzarB, PrakadanSM, WadsworthMH2nd, TreacyD, TrombettaJJ, et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016;352:189–196. 10.1126/science.aad0501 [CrossRef] [PubMed] [Google Scholar]
- FilbinMG, TiroshI, HovestadtV, ShawML, EscalanteLE, MathewsonND, et al. Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science. 2018;360:331–335. 10.1126/science.aao4750 [Google Scholar]
- SuvaML, TiroshI. Single-cell RNA sequencing in cancer: Lessons learned and emerging challenges. Mol Cell. 2019;75:7–12. 10.1016/j.molcel.2019.05.003 [Google Scholar]
- SottorivaA, SpiteriI, PiccirilloSG, TouloumisA, CollinsVP, MarioniJC, et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A. 2013;110:4009–4014. 10.1073/pnas.1219747110 [Google Scholar]
- CeccarelliM, BarthelFP, MaltaTM, SabedotTS, SalamaSR, MurrayBA, et al. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell. 2016;164(3):550–63. 10.1016/j.cell.2015.12.028 [Google Scholar]
- Eckel-PassowJE, LachanceDH, MolinaroAM, WalshKM, DeckerPA, SicotteH, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. New Engl J Med. 2015;372(26):2499–2508. 10.1056/NEJMoa1407279 [Google Scholar]
- Hernandez MartinezA, MadurgaR, Garcia-RomeroN, Ayuso-SacidoA. Unravelling glioblastoma heterogeneity by means of single-cell RNA sequencing. Cancer Lett. 2022;527:66–79. 10.1016/j.canlet.2021.12.008 [Google Scholar]
- SchiffmanJS, D’AvinoAR, PrietoT, PangY, FanY, RajagopalanS, et al. Defining heritability, plasticity, and transition dynamics of cellular phenotypes in somatic evolution. Nat Genet. 2024;56:2174–2184. 10.1038/s41588-024-01920-6 [Google Scholar]
- SuvaML, TiroshI. The glioma stem cell model in the era of single-cell genomics. Cancer Cell. 2020;37:630–636. 10.1016/j.ccell.2020.04.001 [Google Scholar]
- MarallanoVJ, UghettaME, TejeroR, NandaS, RamalingamR, StalbowL, et al. Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines. Sci Rep. 2024;14(1):7246. 10.1038/s41598-024-56102-5 [Google Scholar]
- BvH, JollyMK. Proneural-mesenchymal antagonism dominates the patterns of phenotypic heterogeneity in glioblastoma. iScience. 2024;27:109184. 10.1016/j.isci.2024.109184 [Google Scholar]
- MarzialiG, SignoreM, BuccarelliM., GrandeS., PalmaA., BiffoniM., et al. (2016). Metabolic/proteomic signature defines two glioblastoma subtypes with different clinical outcome. Sci Rep;6:21557. 10.1038/srep21557 [Google Scholar]
- LamKHB, DiamandisP. Niche deconvolution of the glioblastoma proteome reveals a distinct infiltrative phenotype within the proneural transcriptomic subgroup. Sci Data. 2022;9:596. 10.1038/s41597-022-01716-5 [Google Scholar]
- LlagunoA, SunS, PedrazaDAM, VeraE, WangZ., et al. Cell-of-origin susceptibility to glioblastoma formation declines with neural lineage restriction. Nat Neurosci. 2019;22:545–555. 10.1038/s41593-018-0333-8 [Google Scholar]
- BhaduriA, Di LulloE, JungD, MullerS, CrouchEE, EspinosaCS, et al. Outer radial glia-like cancer stem cells contribute to heterogeneity of glioblastoma. Cell Stem Cell. 2020;26:48–63 e46. 10.1016/j.stem.2019.11.015 [Google Scholar]
- VenteicherAS, TiroshI, HebertC, YizhakK, NeftelC, FilbinMG, et al. Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. Science. 2017;355:eaai8478. 10.1126/science.aai8478 [Google Scholar]
- DirkseA, GolebiewskaA, BuderT, NazarovPV, MullerA, PoovathingalS, et al. Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment. Nat Commun. 2019;10:1787. 10.1038/s41467-019-09853-z [Google Scholar]
- HuY, JiangY, BehnanJ, RibeiroMM, KalantziC, ZhangMD, et al. Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages. Sci Adv. 2022;8:eabm6340. 10.1126/sciadv.abm6340 [Google Scholar]
- HamedAA, HuaK, TrinhQM, SimonsBD, MarioniJC, SteinLD, et al. Gliomagenesis mimics an injury response orchestrated by neural crest-like cells. Nature. 2025;638:499–509. 10.1038/s41586-024-08356-2 [Google Scholar]
- XieY, YangF, HeL, HuangH, ChaoM, CaoH, et al. Single-cell dissection of the human blood-brain barrier and glioma blood-tumor barrier. Neuron. 2024;112:3089–3105 e3087. 10.1016/j.neuron.2024.07.026 [Google Scholar]
- GavishA, TylerM, GreenwaldAC, HoefflinR, SimkinD, TschernichovskyR, et al. Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours. Nature. 2023;618:598–606. 10.1038/s41586-023-06130-4 [Google Scholar]
- BaronM, TagoreM, HunterMV, KimIS, MoncadaR, YanY, et al. The stress-like cancer cell state is a consistent component of tumorigenesis. Cell Syst. 2020;11: 536–546 e537. 10.1016/j.cels.2020.08.018 [Google Scholar]
- LucasCG, Al-AdliNN, YoungJS, GuptaR, MorshedRA, WuJ, et al. Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses. Neuro Oncol. 2025;27:89–105. 10.1093/neuonc/noae214 [Google Scholar]
- SchaferN, GielenGH, RauschenbachL, KebirS, TillA, et al. Longitudinal heterogeneity in glioblastoma: Moving targets in recurrent versus primary tumors. J Transl Med. 2019;17:96. 10.1186/s12967-019-1846-y [Google Scholar]
- BejaranoL, LourencoJ, KauzlaricA, LamprouE, CostaCF, GallandS, et al. Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors. Immunity. 2025;58:1015–1032 e1016. 10.1016/j.immuni.2025.02.022 [Google Scholar]
- HeH, YanM, YeK, ShiR, TongL, ZhangS, et al. Predicting prognosis and immunotherapy response in glioblastoma (GBM) with a 5-gene CAF-risk signature. Cancer Rep (Hoboken). 2025;8:e70158. 10.1002/cnr2.70158 [Google Scholar]
- LiuM, JiZ, JainV, SmithVL, HockeE, PatelAP, et al. Spatial transcriptomics reveals segregation of tumor cell states in glioblastoma and marked immunosuppression within the perinecrotic niche. Acta Neuropathol Commun. 2024;12:64. 10.1186/s40478-024-01769-0 [Google Scholar]
- FeldmanL. Hypoxia within the glioblastoma tumor microenvironment: A master saboteur of novel treatments. Front Immunol. 2024;15:1384249. 10.3389/fimmu.2024.1384249 [Google Scholar]
- RibattiD, PezzellaF. Vascular co-option and other alternative modalities of growth of tumor vasculature in glioblastoma. Front Oncol. 2022;12:874554. 10.3389/fonc.2022.874554 [Google Scholar]
- ScholzA, HarterPN, CremerS, YalcinBH, GurnikS, YamajiM, et al. Endothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naive and bevacizumab-resistant glioblastoma. EMBO Mol Med. 2016; 8(1): 39–57. 10.15252/emmm.201505505 [Google Scholar]
- WangW, LiT, ChengY, LiF, QiS, MaoM, et al. Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization. Cancer Cell. 2024;42(5):815–832.e12. 10.1016/j.ccell.2024.03.013 [Google Scholar]
- MathurR, WangQ, SchuppPG, NikolicA, HilzS, HongC, et al. Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective. Cell. 2024;187;446–463 e416. 10.1016/j.cell.2023.12.013 [Google Scholar]
- BaigS, WinklerF. A holistic view of the malignant organism we call glioblastoma. Cell. 2024;187:271–273. 10.1016/j.cell.2023.12.021 [Google Scholar]
- StåhlPL, SalménF, VickovicS, LundmarkA, NavarroJF, MagnussonJ, et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science. 2016;353:78–82. 10.1126/science.aaf2403 [Google Scholar]
- MarxV. Method of the year: Spatially resolved transcriptomics. Nat Methods. 2021;18:9–14. 10.1038/s41592-020-01033-y [Google Scholar]
- RaviVM, WillP, KueckelhausJ, SunN, JosephK, SalieH, et al. Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma. Cancer Cell. 2022;40:639–655 e613. 10.1016/j.ccell.2022.05.009 [Google Scholar]
- RenY, HuangZ, ZhouL, XiaoP, SongJ, HeP, et al. Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas. Nat Commun. 2023;14:1028. 10.1038/s41467-023-36707-6 [Google Scholar]
- BabicD, JovcevskaI, ZottelA. B7–H3 in glioblastoma and beyond: Significance and therapeutic strategies. Front Immunol. 2024;15:1495283. 10.3389/fimmu.2024.1495283 [Google Scholar]
- ChenJ, HuangZ, ChenY, TianH, ChaiP, ShenY, et al. Lactate and lactylation in cancer. Signal Transduct Target Ther. 2025;10:38. 10.1038/s41392-024-02082-x [Google Scholar]
- SattirajuA, KangS, GiottiB, ChenZ, MarallanoVJ, BruscoC, et al. Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression. Immunity. 2023;56:1825–1843 e1826. 10.1016/j.immuni.2023.06.017 [Google Scholar]
- GouZ, SunQ, LiJ. Exploring lactylation and cancer biology: Insights from pathogenesis to clinical applications. Front Cell Dev Biol. 2025;13:1598232. 10.3389/fcell.2025.1598232 [Google Scholar]
- LouisDN, PerryA, WesselingP, BratDJ, CreeIA, Figarella-BrangerD, et al. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro-Oncol. 2021;23(8):1231–1251. 10.1093/neuonc/noab106 [Google Scholar]
- BritoC, AzevedoA, EstevesS, MarquesAR, MartinsC, CostaI, et al. Clinical insights gained by refining the 2016 WHO classification of diffuse gliomas with: EGFR amplification, TERT mutations, PTEN deletion and MGMT methylation. BMC Cancer. 2019;19(1):968. 10.1186/s12885-019-6177-0 [Google Scholar]
- WangH, ZhangX, LiuJ, ChenW, GuoX, WangY, et al. Clinical roles of EGFR amplification in diffuse gliomas: A real-world study using the 2021 WHO classification of CNS tumors. Front Neurosci. 2024;18:1308627. 10.3389/fnins.2024.1308627 [Google Scholar]
- Manendra SinghT, ShrivastavaA. TERT promoter mutations correlate with IDHs, MGMT and EGFR in glioblastoma multiforme. Neurol India. 2021;69(1): 35–136. 10.4103/0028-3886.310071 [Google Scholar]
- HoadleyKA, YauC, HinoueT, WolfDM, LazarAJ, DrillE, et al. Cell-of-origin patterns dominate the molecular classification of 10, 000 tumors from 33 types of cancer. Cell. 2018;173(2):291–304.e6. 10.1016/j.cell.2018.03.022 [Google Scholar]
- FordhamAJ, HacherlCC, PatelN, JonesK, MyersB, AbrahamM, et al. Differentiating glioblastomas from solitary brain metastases: An update on the current literature of advanced imaging modalities. Cancers. 2021;13(12):2960. 10.3390/cancers13122960 [Google Scholar]
- Pombo AntunesAR, ScheyltjensI, LodiF, MessiaenJ, AntoranzA, DuerinckJ, et al. Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization. Nat Neurosci. 2021;24:595–610. 10.1038/s41593-020-00789-y [Google Scholar]
- BagleySJ, DesaiAS, FraiettaJA, SilverbushD, ChafamoD, FreeburgNF, et al. Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Ralpha2 in recurrent glioblastoma: A phase 1 trial. Nat Med. 2025;31:2778–2787. 10.1038/s41591-025-03745-0 [Google Scholar]
- MengQ, ZhangY, LiG, LiY, XieH, ChenX. New insights for precision treatment of glioblastoma from analysis of single-cell lncRNA expression. J Cancer Res Clin Oncol. 2021;147:1881–1895. 10.1007/s00432-021-03584-9 [Google Scholar]
- SaladinoGM, MangarovaDB, NernekliK, WangJ, AnnioG, VarniabZS, et al. Multimodal imaging approach to track theranostic nanoparticle accumulation in glioblastoma with magnetic resonance imaging and intravital microscopy. Nanoscale. 2025;17:9986–9995. 10.1039/d5nr00447k [Google Scholar]
- RahmanMA, JalouliM, YadabMK, Al-ZharaniM. Progress in drug delivery systems based on nanoparticles for improved glioblastoma therapy: Addressing challenges and investigating opportunities. Cancers (Basel). 2025;17:701. 10.3390/cancers17040701 [Google Scholar]
- SharifiM, ChoWC, AnsariesfahaniA, TarharoudiR, MalekisarvarH, SariS, et al. An updated review on EPR-based solid tumor targeting nanocarriers for cancer treatment. Cancers (Basel). 2022;14:2868. 10.3390/cancers14122868 [Google Scholar]
- LiY, ZhaoL, LiXF. The hypoxia-activated prodrug TH-302: exploiting hypoxia in cancer therapy. Front Pharmacol. 2021;12:636892. 10.3389/fphar.2021.636892 [Google Scholar]
- RobinsonSD, FilippopoulouC, BestaS, SamuelsM, BetranAL, Abu AjamiehM, et al. Spatial biology – unravelling complexity within the glioblastoma microenvironment. Trends Mol Med. 2025;31:846–859. 10.1016/j.molmed.2025.01.014 [Google Scholar]
Current usage metrics show cumulative count of Article Views (full-text article views including HTML views, PDF and ePub downloads, according to the available data) and Abstracts Views on Vision4Press platform.
Data correspond to usage on the plateform after 2015. The current usage metrics is available 48-96 hours after online publication and is updated daily on week days.
Initial download of the metrics may take a while.
