Glioblastoma (GBM) is a primary tumor of the brain defined by its uniform lethality and resistance to conventional therapies. There have been considerable efforts to untangle the metabolic underpinnings of this disease to find novel therapeutic avenues for treatment. An emerging focus in this field is fatty acid (FA) metabolism, which is critical for numerous diverse biological processes involved in GBM pathogenesis. These processes can be classified into four broad fates: anabolism, catabolism, regulation of ferroptosis, and the generation of signaling molecules. Each fate provides a unique perspective by which we can inspect GBM biology and gives us a road map to understanding this complicated field. This Review discusses the basic, translational, and clinical insights into each of these fates to provide a contemporary understanding of FA biology in GBM. It is clear, based on the literature, that there are far more questions than answers in the field of FA metabolism in GBM, and substantial efforts should be made to untangle these complex processes in this intractable disease.
Jason Miska, Navdeep S. Chandel
Title and authors | Publication | Year |
---|---|---|
Multiparametric MRI along with machine learning predicts prognosis and treatment response in pediatric low-grade glioma
Fathi Kazerooni A, Kraya A, Rathi KS, Kim MC, Vossough A, Khalili N, Familiar AM, Gandhi D, Khalili N, Kesherwani V, Haldar D, Anderson H, Jin R, Mahtabfar A, Bagheri S, Guo Y, Li Q, Huang X, Zhu Y, Sickler A, Lueder MR, Phul S, Koptyra M, Storm PB, Ware JB, Song Y, Davatzikos C, Foster JB, Mueller S, Fisher MJ, Resnick AC, Nabavizadeh A |
Nature Communications | 2025 |
TRAF3 loss protects glioblastoma cells from lipid peroxidation and immune elimination via dysregulated lipid metabolism
Yu Zeng, Liqian Zhao, Kunlin Zeng, Ziling Zhan, Zhengming Zhan, Shangbiao Li, Hongchao Zhan, Peng Chai, Cheng Xie, Shengfeng Ding, Yuxin Xie, Li Wang, Cuiying Li, Xiaoxia Chen, Daogang Guan, Enguang Bi, Jian-you Liao, Fan Deng, Xiaochun Bai, Ye Song, Aidong Zhou |
Journal of Clinical Investigation | 2025 |
Comprehensive analysis reveals cholesterol metabolism-related signature for predicting prognosis and guiding individualized treatment of glioma
Lu D, Wang F, Yang Y, Duan A, Ren Y, Feng Y, Teng H, Chen Z, Sun X, Wang Z |
Heliyon | 2025 |
Global research landscape and hotspots for ferroptosis in glioma: A comprehensive bibliometric and visual analysis
Zheng X, Diao M, Tong S, Yang S, Lin J, Zhuo S, Wang T, Dai J, Chen S, Wang K |
Heliyon | 2025 |
A Pilot Study on Qualitative Metabolomics to Characterize Lewis Lung Carcinoma in Mice
Stawarska A, Bamburowicz-Klimkowska M, Pisklak DM, Gawlak M, Grudzinski IP |
Life | 2025 |
Constructing a Glioblastoma Prognostic Model Related to Fatty Acid Metabolism Using Machine Learning and Identifying F13A1 as a Potential Target
Liu Y, Deng H, Song P, Zhang M |
Biomedicines | 2025 |
Metabolic crossroads: unravelling immune cell dynamics in gastrointestinal cancer drug resistance
Suri C, Pande B, Suhasini Sahithi L, Swarnkar S, Khelkar T, Verma HK |
Cancer Drug Resistance | 2025 |
Lipid metabolism: the potential therapeutic targets in glioblastoma
Lu L, Zhang Y, Yang Y, Jin M, Ma A, Wang X, Zhao Q, Zhang X, Zheng J, Zheng X |
Cell Death Discovery | 2025 |
Metabolic profiling of adult and pediatric gliomas reveals enriched glucose availability in pediatric gliomas and increased fatty acid oxidation in adult gliomas
Sviderskiy VO, Vasudevaraja V, Dubois LG, Stafford J, Liu EK, Serrano J, Possemato R, Snuderl M |
Acta Neuropathologica Communications | 2025 |
Fatty acid synthase inhibitor cerulenin attenuates glioblastoma progression by reducing EMT and stemness phenotypes, inducing oxidative and ER stress response, and targeting PI3K/AKT/NF-κB axis
Pekmez M, Mete ŞB, Aksüt Y, Öğütcü İ, Baştürk FN, Gerçek YC, Şengelen A |
Medical Oncology (Northwood, London, England) | 2025 |
Lipid peroxidation and immune activation: TRAF3’s double-edged strategy against glioblastoma
Chia TY, Sadagopan NS, Miska J |
The Journal of Clinical Investigation | 2025 |
Praja2 controls P-body assembly and translation in glioblastoma by non-proteolytic ubiquitylation of DDX6.
Senatore E, Avolio R, Rinaldi L, Chiuso F, Oliva MA, D'Ambrosio C, Bianco AG, Dalla E, Pagnotta SM, Flammia R, Ambrosino C, Memoli D, Turacchio G, Mimoune SI, Toiron Y, Audebert S, Camoin L, Lignitto L, Scaloni A, Arcella A, Feliciello A |
EMBO reports | 2025 |
GLIO-Select: Machine Learning-Based Feature Selection and Weighting of Tissue and Serum Proteomic and Metabolomic Data Uncovers Sex Differences in Glioblastoma.
Tasci E, Chappidi S, Zhuge Y, Zhang L, Cooley Zgela T, Sproull M, Mackey M, Camphausen K, Krauze AV |
International journal of molecular sciences | 2025 |
APOL4-mediated intracellular cholesterol trafficking is essential for glioblastoma cell growth
Zhang M, Yang T, Qian Y |
BMC Cancer | 2025 |
From Biomarker Discovery to Clinical Applications of Metabolomics in Glioblastoma
Šamec N, Krapež G, Skubic C, Jovčevska I, Videtič Paska A |
Metabolites | 2025 |
Myeloid Metabolism and Its Exploitative Potential for Immunotherapy in Cancer
Corey Dussold1,2, Kaylee Zilinger1,2, Jillyn Turunen1,2, Amy B. Heimberger1,2, Jason Miska,1,2 |
Journal of Clinical Investigation | 2024 |
High-throughput CRISPR technology: a novel horizon for solid organ transplantation
Li X, Chen Z, Ye W, Yu J, Zhang X, Li Y, Niu Y, Ran S, Wang S, Luo Z, Zhao J, Hao Y, Zong J, Xia C, Xia J, Wu J |
Frontiers in immunology | 2024 |
Emerging Lipid Targets in Glioblastoma
Darwish A, Pammer M, Gallyas F Jr, Vígh L, Balogi Z, Juhász K |
Cancers | 2024 |
Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK
Guo F, Ling G, Qiu J, Li J, Gan Y, Yu Y, Tang J, Mo L, Piao H |
Chinese medicine | 2024 |
13C-SpaceM: Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer
Buglakova E, Ekelöf M, Schwaiger-Haber M, Schlicker L, Molenaar MR, Mohammed S, Stuart L, Eisenbarth A, Hilsenstein V, Patti GJ, Schulze A, Snaebjornsson MT, Alexandrov T |
2024 | |
Identification and Validation of a PEX5-Dependent Signature for Prognostic Prediction in Glioma.
Qin X, Wang B, Lu X, Song Y, Wang W |
Biomolecules | 2024 |
Spatially Resolved Microglia/Macrophages in Recurrent Glioblastomas Overexpress Fatty Acid Metabolism and Phagocytic Genes.
Mistry AM, Daneshmand J, Seo SJ, Lehman NL, Miller DM, Goodin DA, Frieboes HB, Chen J, Masters A, Williams BJ, Yaddanapudi K |
Current oncology (Toronto, Ont.) | 2024 |
Biological Insights and Radiation–Immuno–Oncology Developments in Primary and Secondary Brain Tumors
Gregucci F, Beal K, Knisely JP, Pagnini P, Fiorentino A, Bonzano E, Vanpouille-Box CI, Cisse B, Pannullo SC, Stieg PE, Formenti SC |
Cancers | 2024 |
A targetable PRR11-DHODH axis drives ferroptosis- and temozolomide-resistance in glioblastoma
Miao Z, Xu L, Gu W, Ren Y, Li R, Zhang S, Chen C, Wang H, Ji J, Chen J |
Redox Biology | 2024 |
Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges.
Seyhan AA |
International journal of molecular sciences | 2024 |
ALOX5 contributes to glioma progression by promoting 5-HETE-mediated immunosuppressive M2 polarization and PD-L1 expression of glioma-associated microglia/macrophages.
Chen T, Liu J, Wang C, Wang Z, Zhou J, Lin J, Mao J, Pan T, Wang J, Xu H, He X, Wu D, Liu Z |
Journal for immunotherapy of cancer | 2024 |
Biological Evaluation of Lysionotin: a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma.
Shao XX, Chen C, Liu J, Li QJ, He S, Qi XH, Fu XJ, Wang ZG |
Chinese journal of integrative medicine | 2024 |
The proto-oncogene tyrosine kinase c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis.
Zhao W, Ouyang C, Zhang L, Wang J, Zhang J, Zhang Y, Huang C, Xiao Q, Jiang B, Lin F, Zhang C, Zhu M, Xie C, Huang X, Zhang B, Zhao W, He J, Chen S, Liu X, Lin D, Li Q, Wang Z |
Nature communications | 2024 |
Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer
Buglakova E, Ekelöf M, Schwaiger-Haber M, Schlicker L, Molenaar MR, Shahraz M, Stuart L, Eisenbarth A, Hilsenstein V, Patti GJ, Schulze A, Snaebjornsson MT, Alexandrov T |
Nature Metabolism | 2024 |
Metabolism: an important player in glioma survival and development
Wang N, Yuan Y, Hu T, Xu H, Piao H |
Discover Oncology | 2024 |
The acyltransferase transmembrane protein 68 regulates breast cancer cell proliferation by modulating triacylglycerol metabolism.
Zhao Z, Pang H, Yu Q, Zeng F, He X, Sun Q, Chang P |
Lipids in health and disease | 2024 |
Spatiotemporal evolutionary process of osteosarcoma immune microenvironment remodeling and C1QBP‐driven drug resistance deciphered through single‐cell multi‐dimensional analysis
Wu X, Tang N, Zhao Q, Xiong J |
Bioengineering & Translational Medicine | 2024 |
Starting points for the development of new targeted therapies for glioblastoma multiforme
Rusak A, Wiatrak B, Krawczyńska K, Górnicki T, Zagórski K, Zadka Ł, Fortuna W |
Translational Oncology | 2024 |
The Role and Applied Value of Mitochondria in Glioma‐Related Research
Chen L, Zhang H, Shang C, Hong Y |
CNS Neuroscience & Therapeutics | 2024 |
Metabolic Barriers to Glioblastoma Immunotherapy
Choudhary N, Osorio RC, Oh JY, Aghi MK |
Cancers | 2023 |
Bacteria associated with glioma: a next wave in cancer treatment
Meng Y, Sun J, Zhang G, Yu T, Piao H |
Frontiers in Cellular and Infection Microbiology | 2023 |
Metabolic Profiles Point Out Metabolic Pathways Pivotal in Two Glioblastoma (GBM) Cell Lines, U251 and U-87MG.
Martins F, van der Kellen D, Gonçalves LG, Serpa J |
Biomedicines | 2023 |
Dysregulated lipid metabolism in TMZ-resistant glioblastoma: pathways, proteins, metabolites and therapeutic opportunities.
Kao TJ, Lin CL, Yang WB, Li HY, Hsu TI |
Lipids in Health and Disease | 2023 |
C1q+ tumor-associated macrophages contribute to immunosuppression through fatty acid metabolic reprogramming in malignant pleural effusion
Zhang S, Peng W, Wang H, Xiang X, Ye L, Wei X, Wang Z, Xue Q, Chen L, Su Y, Zhou Q |
Journal for ImmunoTherapy of Cancer | 2023 |
Metabolic partitioning in the brain and its hijacking by glioblastoma
de Ruiter Swain J, Michalopoulou E, Noch EK, Lukey MJ, Van Aelst L |
Genes & development | 2023 |
Prognosis and immunoinfiltration analysis of angiogene-related genes in grade 4 diffuse gliomas
Liu H, Zeng Z, Sun P |
Aging | 2023 |
FHOD1 is upregulated in glioma cells and attenuates ferroptosis of glioma cells by targeting HSPB1 signaling
Zhang F, Wu L, Feng S, Zhao Z, Zhang K, Thakur A, Xu Z, Liang Q, Liu Y, Liu W, Yan Y |
CNS Neuroscience & Therapeutics | 2023 |
Liquid biopsy: creating opportunities in brain space
Trivedi R, Bhat KP |
British Journal of Cancer | 2023 |
BMP signaling in cancer stemness and differentiation.
Zhou W, Yan K, Xi Q |
2023 |