bims-meract 2025-10-12 papers

bims-meract

Biomed News

on Metabolic reprogramming and anti-cancer therapy

Issue of 2025–10–12
eleven papers selected by
Andrea Morandi, Università degli Studi di Firenze

Targeting SREBP-dependent lipogenesis potentiates the anti-tumor activity of docetaxel by increasing membrane permeability and intracellular drug accumulation.
Non-canonical dihydrolipoyl transacetylase promotes chemotherapy resistance via mitochondrial tetrahydrofolate signaling.
SART3 Activates CD36 Transcription by Recruiting FOXM1 and Activates PARP to Augment Cisplatin Resistance in Non-Small Cell Lung Cancer.
The deubiquitylase OTUB1 drives gemcitabine resistance in pancreatic cancer by enhancing pyrimidine metabolism through modulating DHODH mRNA stability.
Dissection of immunotherapeutic predictive versus prognostic transcriptional programs identifies SLC22A5-centric carnitine metabolism-driven resistance to anti-PD-(L)1 treatment in non-small cell lung cancer.
SENP1 drives glycolysis and cisplatin resistance in gastric cancer via desumoylating ENO1.
Integration of Metabolic Profiling and Functional Genomics Suggests IGJ as a Driver of Chemoresistance in B-ALL.
Targeting sterol O-acyltransferase 1 rewires fatty acid metabolism and uncovers immune vulnerability in hepatocellular carcinoma.
MTAP deficiency confers resistance to cytosolic nucleic acid sensing and STING agonists.
Targeting ESR1 restores SQSTM1-dependent autophagy and sensitizes ER-positive breast cancer to oxidative and radiation stress.
Harnessing ferroptosis to transform glioblastoma therapy and surmount treatment resistance.

Oncogene. 2025 Oct 04.

Targeting SREBP-dependent lipogenesis potentiates the anti-tumor activity of docetaxel by increasing membrane permeability and intracellular drug accumulation.

Jiaqi Chen, Mu-En Wang, Alyssa R Bawcom, Yi Lu, John M Asara, Lei Li, Ming Chen.

Lipid metabolism is among the most frequently dysregulated metabolic processes in human cancer, yet how cellular lipids, the end products of lipogenesis, and their composition are altered to support various aspects of cancer remains poorly understood. Here, we show that targeting SREBP-dependent lipogenesis via FGH10019, an orally available SREBP inhibitor, enhances docetaxel-induced cytotoxicity in human prostate cancer cells in vitro and in vivo. Mechanistically, suppression of lipid biosynthesis leads to a shift in cellular lipid composition toward polyunsaturated lipids, resulting in increased membrane permeability and intracellular docetaxel accumulation. Thus, our findings reveal a critical role of de novo lipogenesis in protecting cancer cells from chemotherapeutics and suggest that treatment with lipogenesis inhibitors could improve the efficacy of chemotherapy against human prostate cancer.

DOI: https://doi.org/10.1038/s41388-025-03588-6
Nat Commun. 2025 Oct 08. 16(1): 8932

Non-canonical dihydrolipoyl transacetylase promotes chemotherapy resistance via mitochondrial tetrahydrofolate signaling.

Jung Seok Hwang, JiHoon Kang, Jaehyun Kim, Kiyoung Eun, Sophia West, Hannah E Bacho, Vanessa Avalos, Sydney Shuff, Dong M Shin, Nabil F Saba, Kelly R Magliocca, Cheng-Kui Qu, Haian Fu, Suresh S Ramalingam, Andrey A Ivanov, Taro Hitosugi, Sumin Kang.

Chemotherapy is often a primary treatment for cancer. However, resistance leads to therapeutic failure. Acetylation dynamics play important regulatory roles in cancer cells, but the mechanisms by which acetylation mediates therapy resistance remain poorly understood. Here, using acetylome-focused RNA interference (RNAi) screening, we find that acetylation induced by mitochondrial dihydrolipoyl transacetylase (DLAT), independent of the pyruvate dehydrogenase complex, is pivotal in promoting resistance to chemotherapeutics, such as cisplatin. Mechanistically, DLAT acetylates methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) at lysine 44 and promotes 10-formyl-tetrahydrofolate (10-formyl-THF) and consequent mitochondrially encoded cytochrome c oxidase II (MT-CO2) induction. DLAT signaling is elevated in cancer patients refractory to chemotherapy or chemoimmunotherapy. A decoy peptide DMp39, designed to target DLAT signaling, effectively sensitizes cancer cells to cisplatin in patient-derived xenograft models. Collectively, our study reveals the crucial role of DLAT in shaping chemotherapy resistance, which involves an interplay between acetylation signaling and metabolic reprogramming, and offers a unique decoy peptide technology to overcome chemotherapy resistance.

DOI: https://doi.org/10.1038/s41467-025-63892-3
Am J Respir Cell Mol Biol. 2025 Oct 10.

SART3 Activates CD36 Transcription by Recruiting FOXM1 and Activates PARP to Augment Cisplatin Resistance in Non-Small Cell Lung Cancer.

Wenhui Huang, Bin Bi, Qilan Huang, Haijing Wu, Xinghan Cheng, Li Pan.

Cisplatin resistance remains a major barrier to effective lung cancer treatment. In this study, we identified that SART3 is upregulated in cisplatin-resistant non-small cell lung cancer (NSCLC) cells and promotes DNA damage repair. SART3 deletion sensitized cells to cisplatin, whereas re-expression restored resistance. Mechanistically, SART3 enhanced DNA repair mainly through the PARP pathway rather than ATM or DNA-PK, and its deletion increased gH2AX levels and reduced BrdU incorporation. Metabolic analysis revealed that SART3-driven resistance relied on elevated fatty acid (FA) β-oxidation rather than glycolysis. SART3 promoted FA uptake by upregulating CD36, resulting in increased oxidative phosphorylation, ATP production, and enhanced DNA repair. Targeting FA metabolism with CPT1A inhibitors or CD36 antagonists, or blocking PARP activity, significantly reversed SART3-mediated resistance. Further, SART3 recruited FOXM1 to activate CD36 transcription by modulating H2b deubiquitination. In vivo, inhibition of the SART3-CD36-PARP axis effectively suppressed tumor growth and restored cisplatin sensitivity. Collectively, our findings reveal that SART3-driven metabolic reprogramming and DNA repair underpin cisplatin resistance, providing potential therapeutic strategies to overcome drug resistance in NSCLC.

DOI: https://doi.org/10.1165/rcmb.2025-0319OC
Cell Death Dis. 2025 Oct 06. 16(1): 697

The deubiquitylase OTUB1 drives gemcitabine resistance in pancreatic cancer by enhancing pyrimidine metabolism through modulating DHODH mRNA stability.

Wenming Zhang, Rui Liu, Junwen Hu, Shuangyan Wan, Yeqin Zou, Tong Che, Jin Zhang, Leifeng Chen, Xiaogang Peng.

Gemcitabine resistance is a major clinical challenge in pancreatic cancer (PC); therefore, strategies to combat gemcitabine resistance are urgently required. Reprogramming pyrimidine metabolism by oncogenic signaling contributes to cancer progression and confers chemoresistance to many cancers. The current study identified the deubiquitinating enzyme OTUB1 as a promising therapeutic target for combating gemcitabine resistance in PC. OTUB1 was found to be aberrantly expressed in PC and remarkably correlated with poor patient survival. Both in vivo and in vitro, OTUB1 knockdown increased the gemcitabine efficacy of PC cells by inhibiting pyrimidine metabolism. Furthermore, OTUB1 enhanced de novo nucleotide pyrimidine synthesis in PC cells by upregulating dihydroorotate dehydrogenase (DHODH), a critical rate-limiting enzyme for pyrimidine de novo biosynthesis. Mechanistically, OTUB1 suppressed the degradation and polyubiquitination of the RNA-binding protein DEAD-box helicase 3 X-linked (DDX3X), which in turn stabilized DDX3X-mediated DHODH mRNA. OTUB1 interacts with DDX3X, and the binding stabilizes DDX3X through its deubiquitinase activity. In addition, a small-molecule OTUB1 inhibitor combined with gemcitabine treatment could synergistically inhibit tumor growth in high-OTUB1-expressing murine tumoroids. Collectively, OTUB1 could impart gemcitabine resistance by promoting de novo pyrimidine synthesis, and targeted suppression of OTUB1 could be an effective strategy to overcome gemcitabine resistance in PC.

DOI: https://doi.org/10.1038/s41419-025-08001-4
Drug Resist Updat. 2025 Sep 29. pii: S1368-7646(25)00116-5. [Epub ahead of print]84 101313

Dissection of immunotherapeutic predictive versus prognostic transcriptional programs identifies SLC22A5-centric carnitine metabolism-driven resistance to anti-PD-(L)1 treatment in non-small cell lung cancer.

Yu-Ze Wang, Ning Gao, Zhanwen Lin, Si-Heng Wang, Shichang Ai, Zhanqi Wei, Shuishen Zhang, Junchao Cai, Weixiong Yang, Si-Cong Ma, Chao Cheng.

   AIMS: Prognostic and predictive biomarkers are two common biomarker types in clinics, with the former indicating the natural course of cancer regardless of treatment, and the latter determining the response to a specific regimen. Understanding the predictive versus prognostic effect of biomarkers is essential to understand treatment-specific response from the inherent prognosis of cancer. Herein, we aimed to uncover the predictive metabolic signatures specific to immunotherapy resistance by distinguishing the predictive versus prognostic effect of transcriptional programs in advanced non-small cell lung cancer (NSCLC) treated with immunotherapy.
METHODS: Clinical and transcriptomic data were collected from two randomized controlled trials, OAK (n = 699, discovery cohort) and POPLAR (n = 192, validation cohort) comparing immunotherapy with chemotherapy. Metabolic transcriptional signature scores were calculated through gene set variation analysis. Cox regression and interaction test were conducted to differentiate the predictive versus prognostic effect. Additionally, lung tumor-bearing murine models were established using Slc22a5-overexpressing (OE) and control Lewis Lung Carcinoma (LLC) cells, and treated with immunotherapy or chemotherapy. The translational potential of an SLC22A5 (Solute Carrier Family 22 Member 5) inhibitor in combination with immunotherapy was assessed in preclinical setting. The tumor microenvironment was analyzed by flow cytometry, immunofluorescence, and Enzyme-Linked Immunosorbent Assay (ELISA) to validate the mechanistic findings.
RESULTS: Metabolic transcriptional programs were divided into four categories based on different predictive effects specific to immunotherapy or chemotherapy, among which carnitine metabolism stood out as the most prominent metabolic process contributing to the resistance to immunotherapy. Specifically, SLC22A5 as the only high-affinity carnitine transporter was remarkably upregulated in immunotherapy-resistant patients. The predictive effect of SLC22A5-centric carnitine metabolism for resistance to immunotherapy rather than chemotherapy was independently validated in an external randomized trial. Critically, preclinical models revealed that Slc22a5 overexpression drove resistance to immunotherapy but not chemotherapy, by fostering an immunosuppressive microenvironment characterized by M2 macrophage accumulation and CD8 + T cell exclusion. Furthermore, pharmacological inhibition of SLC22A5 by meldonium reshaped the tumor microenvironment toward a more inflamed state and re-sensitized resistant tumors to immunotherapy.
CONCLUSIONS: Our study elucidates the predictive versus prognostic effect of metabolic pathways in advanced NSCLC under immunotherapy. Tumor-intrinsic carnitine metabolism may predict and drive immunotherapy resistance, and targeting SLC22A5-mediated carnitine metabolism could be used to overcome resistance in advanced NSCLC.

Keywords:  Carnitine metabolism; Immunotherapy; Non-small cell lung cancer; Predictive versus prognostic; Resistance

DOI:  https://doi.org/10.1016/j.drup.2025.101313
J Exp Clin Cancer Res. 2025 Oct 08. 44(1): 285

SENP1 drives glycolysis and cisplatin resistance in gastric cancer via desumoylating ENO1.

Yuan Fang, Yunru Gu, Tingting Xu, Peng Wang, Xi Wu, Haoyang Shen, Yangyue Xu, Zixiang Xu, Lei Cao, Xiao Li, Hao Wu, Yongqian Shu, Pei Ma.

   BACKGROUND: Gastric cancer remains a leading cause of cancer-related mortality in world, with advanced-stage patients facing poor prognosis despite emerging therapies. SUMOylation modification is a major post-translation modification, which is essential for cellular behaviors. However, the potential function of SUMOylation in gastric cancer (GC) and the underlying molecular mechanisms remain unclear.
METHODS: In our study, a bioinformatics analysis was conducted to screen potential regulators within the SUMO-Specific Peptidase (SENP) family in GC. In vitro functional experiments including CCK8, colony formation, transwell assay, sphere formation, Glycolytic flux, ECAR and OCR and several animal models including GC xenografts, organoids and lung metastasis models were employed to ascertain the role of SENP1 in GC progression and metastasis. Mass spectrometry analysis, coimmunoprecipitation and immunofluorescence staining were performed to elucidate the mechanisms by which SENP1 functions in GC cells.
RESULTS: We identified that SENP1 was upregulated in GC tissues and correlated with a poor prognosis. Multiple functional experiments demonstrated that SENP1 promotes the proliferation, migration, stemness and glycolysis of GC cells. Mechanistically, SENP1 binds to α-enolase (ENO1) and deSUMOylates the SUMO sites (K256, K394) of SUMO2-modified ENO1, enhancing ENO1 stability and drive gastric tumorigenesis. Meanwhile, SENP1 inhibitor Momordin Ιc (Mc) in combination with cisplatin has a synergistic effect on gastric tumor growth in vitro and in vivo.
CONCLUSION: SENP1 facilitates gastric cancer progression by metabolic reprogramming. Targeting SENP1 with Momordin Ic is a novel therapeutic approach for GC patients.

Keywords:  Cisplatin; Gastric cancer; Glycolysis; SENP1; SUMOylation

DOI:  https://doi.org/10.1186/s13046-025-03543-z
Pediatr Blood Cancer. 2025 Oct 06. e32068

Integration of Metabolic Profiling and Functional Genomics Suggests IGJ as a Driver of Chemoresistance in B-ALL.

Karen Lizeth Pachón-Meza, Camilo Ernesto Moreno-Cristancho, José Luis Padilla-Agudelo, Ana Isabel Ramos-Murillo, Diana Londoño-Barbosa, Gustavo Salguero, Sandra Milena Sanabria-Barrera, Claudia Chica, Nataly Cruz-Rodriguez, Rubén Darío Godoy-Silva, José Arturo Gutiérrez-Triana.

   BACKGROUND: B-cell precursor acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy characterized by the uncontrolled proliferation of immature B lymphoblasts. Despite significant advancements in treatment, chemoresistance remains a major challenge. Previous studies, including those involving Colombian patient cohorts, have identified a gene signature involving ID1, ID3, and IGJ, which correlates with poor prognosis; however, the underlying mechanisms remain unclear. This study integrates metabolic profiling with gene expression analysis of ID1, ID3, and IGJ in patient-derived lymphoblasts. It explores the role of IGJ overexpression in NALM-6 cells to assess its potential contribution to chemoresistance.
METHODS: Bone marrow samples from 33 newly diagnosed B-ALL patients were analyzed for ID1, ID3, and IGJ gene expression. Seahorse XF metabolic assays were conducted on 13 patient samples to assess mitochondrial respiration and glycolytic function. Functional studies were performed in the NALM-6 B-ALL cell line using CRISPRa-mediated IGJ overexpression, followed by metabolic and chemoresistance assays using resazurin-based viability testing with key chemotherapeutic agents.
RESULTS: Patient-derived lymphoblasts exhibited a quiescent metabolic phenotype, with two distinct metabolic subgroups based on oxygen consumption and glycolysis rates. Higher IGJ expression was significantly associated with the glycolytic subgroup and correlated with worse event-free survival (EFS, p = 0.0179) and overall survival (OS, p = 0.0205). In NALM-6 cells, IGJ overexpression led to increased metabolic activity and conferred resistance to dexamethasone, cytarabine, doxorubicin, and methotrexate, but not cyclophosphamide.
CONCLUSION: IGJ upregulation promotes metabolic reprogramming and chemoresistance in B-ALL, suggesting a potential role for IGJ as a biomarker and therapeutic target in overcoming treatment resistance. These findings provide new insights into the metabolic mechanisms underlying B-ALL progression and highlight IGJ as a candidate for future targeted interventions.

Keywords:  B‐cell precursor acute lymphoblastic leukemia; CRISPRa; drug resistance; metabolism; mitochondrial respiration

DOI:  https://doi.org/10.1002/pbc.32068
Hepatology. 2025 Oct 09.

Targeting sterol O-acyltransferase 1 rewires fatty acid metabolism and uncovers immune vulnerability in hepatocellular carcinoma.

Huanhuan Ma, Vanilla Xin Zhang, Yu Man Tsui, Joyce Man-Fong Lee, Eva Lee, Jingyi Lu, Huan Deng, Fanhong Zeng, Daniel Wai-Hung Ho, Charry Hui, Abdullah Husain, Karen Man-Fong Sze, Irene Oi-Lin Ng.

   BACKGROUND AND AIMS: The development of hepatocellular carcinoma (HCC) is intricately linked to metabolic processes and immune evasion strategies. As an emerging metabolic vulnerability in HCC, detailed molecular mechanisms of Sterol O-Acyltransferase 1 (SOAT1) and its role in immune regulation remain unclear. This study aimed to elucidate the mechanism involved and evaluate the potential of SOAT1 as a therapeutic target.
APPROACH AND RESULTS: We explored the role of SOAT1 using genetical and pharmaceutical inhibition in cell lines, patient-derived organoids, and mouse models. Co-culture systems, flow cytometry, and immunohistochemistry were employed to assess tumor-immune interactions. Multi-omics were performed to elucidate the underlying molecular mechanisms. The efficacy of inhibiting SOAT1 alone and in combination with anti-PD1 therapy in vivo was tested. SOAT1 was significantly upregulated in HCC tumors and associated with increased tumorigenicity and immune evasive characteristics. SOAT1 deficiency disrupted lipid homeostasis, leading to the accumulation of saturated fatty acids, reactive oxygen species, and endoplasmic reticulum stress, followed by NF-κB activation. This signaling triggered the production of pro-inflammatory cytokines, adhesion molecules, and the recruitment of CD11c⁺ antigen-presenting cells and cytotoxic CD8⁺ T cells into tumors. Moreover, SOAT1 knockout reduced tumor burden, and the combination of SOAT1 inhibition with PD-1 blockade exhibited synergistic anti-tumor effects.
CONCLUSION: SOAT1 functions as both a metabolic vulnerability and an immune regulator in HCC. Its inhibition disrupts tumor-promoting metabolic processes while enhancing immune activation, presenting it as a promising therapeutic target. Combining SOAT1 inhibition with PD-1 blockade holds potential for improving outcomes in HCC immunotherapy.

Keywords:  NF-κB; SOAT1; cytokines; endoplasmic reticulum stress; immune evasion; lipid metabolism

DOI:  https://doi.org/10.1097/HEP.0000000000001561
Science. 2025 Oct 09. 390(6769): eadl4089

MTAP deficiency confers resistance to cytosolic nucleic acid sensing and STING agonists.

Jung-Mao Hsu, Chunxiao Liu, Weiya Xia, Chung-Yu Chen, Wei-Chung Cheng, Junwei Hou, Mien-Chie Hung.

Cytosolic nucleic acid-sensing pathways are potential targets for cancer immunotherapy. Although stimulator of interferon genes (STING) agonists have shown substantial antitumor effects in animal models, their clinical efficacy in human tumors remains unclear. Deletion of methylthioadenosine phosphorylase (MTAP) is a common genomic alteration in human tumors but is rare in preclinical syngeneic mouse models. We found that homozygous MTAP deletion in human tumors creates a tumor microenvironment that obstructs cytosolic nucleic acid-sensing pathways by down-regulating interferon regulatory factor 3 (IRF3), leading to resistance to STING agonists. Targeting polyamine biosynthesis reverses IRF3 down-regulation, restoring sensitivity to STING agonists in MTAP-deficient tumors. Our findings suggest that MTAP genetic status may inform patient responses to STING agonist therapy and offer an alternative strategy for boosting antitumor immune responses using STING agonists in MTAP-deleted tumors.

DOI: https://doi.org/10.1126/science.adl4089
Cell Death Discov. 2025 Oct 07. 11(1): 451

Targeting ESR1 restores SQSTM1-dependent autophagy and sensitizes ER-positive breast cancer to oxidative and radiation stress.

Yi-Fang Yang, Zhao-Jing He, Han-Hsi Kuo, Yu-Yu Lin, Cheorl-Ho Kim, Huei-Yu Cai, Chi-Long Chen, Michael Hsiao, Ying-Chung Chen, Peter Mu-Hsin Chang, Yu-Chan Chang.

Estrogen receptor-positive (ER⁺) breast cancer is commonly treated with hormone therapy; however, these tumors frequently develop drug resistance and exhibit poor responses to radiotherapy. To investigate the molecular basis of therapy resistance, we explored the role of estrogen receptor alpha (ESR1) in modulating sensitivity to oxidative and radiation stress. Through integrative analysis of publicly available datasets, we identified ESR1 as a key molecular marker associated not only with breast cancer classification but also with radiosensitivity. In ER⁺ breast cancer cell lines, higher endogenous ESR1 expression correlated with increased resistance to ionizing radiation. Functional studies using ESR1 overexpression and knockdown models revealed that depletion of ESR1 sensitized cells to radiation-induced DNA damage, impaired DNA repair efficiency, and reduced clonogenic survival. Notably, we found that the ESR1-SQSTM1 (p62) interaction impairs autophagic flux, contributing to treatment resistance. Mechanistically, ESR1 translocates to the cytoplasm and binds to SQSTM1, thereby disrupting autophagosome maturation. Furthermore, estradiol enhances ESR1 phosphorylation and its affinity for SQSTM1, reinforcing this inhibitory effect on autophagy and promoting resistance to radiation. Our findings uncover a previously unrecognized ESR1-SQSTM1 axis that governs autophagy and redox response in ER⁺ breast cancer. Targeting this pathway may restore sensitivity to radiotherapy and offer a new therapeutic strategy. Assessment of ESR1 expression and autophagy activity may serve as predictive biomarkers for treatment response in ER⁺ breast cancer patients.

DOI: https://doi.org/10.1038/s41420-025-02755-8
Cell Death Discov. 2025 Oct 07. 11(1): 448

Harnessing ferroptosis to transform glioblastoma therapy and surmount treatment resistance.

Shilpi Singh, Iteeshree Mohapatra, Debashis Barik, Haoyi Zheng, Stefan Kim, Mayur Sharma, Clark C Chen, Gatikrushna Singh.

Glioblastoma remains the most aggressive and treatment-resistant brain malignancy, driven by genetic heterogeneity, metabolic plasticity, and an immunosuppressive tumor microenvironment (TME). Current therapies rely on inducing tumor cell death through DNA damage; however, glioma stem cells (GSCs) upregulate compensatory DNA repair pathways, promoting resistance and tumor recurrence. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, offers a novel therapeutic strategy to overcome therapy resistance by exploiting glioblastoma's metabolic vulnerabilities. Unlike conventional therapies, ferroptosis bypasses DNA repair mechanisms, making it particularly effective against therapy-resistant GSCs. It reduces tumor growth by triggering iron-catalyzed oxidative stress, disrupting lipid metabolism, and pushing glioblastoma cells beyond their oxidative threshold. However, resistance mechanisms to ferroptosis, including iron metabolism regulators (IREB2 and ferritinophagy), lipid peroxidation enzymes (ACSL4 and ALOXs), and protective pathways (cystine transporters and glutathione peroxidase 4), limit its therapeutic potential. Extracellular vesicle-mediated iron transfer further contributes to ferroptosis resistance, fostering chemoresistance and radio-resistance. Beyond direct tumor killing, ferroptosis modulates the TME by releasing damage-associated molecular patterns, inducing reactive oxygen species, stimulating CD8+ T-cell activation, enhancing immune checkpoint blockade efficacy, and reprogramming tumor-associated macrophages toward an anti-tumor phenotype. Ferroptosis-based strategies, including glutathione peroxidase 4 inhibitors, nanoparticle-mediated iron delivery, and RNA-based therapies, offer promising avenues for enhancing glioblastoma treatment efficacy. This review highlights ferroptosis as a promising strategy for overcoming glioblastoma resistance by integrating it with chemotherapy, radiotherapy, and immunotherapy to enhance treatment efficacy. Given the complexity of glioblastoma, personalized ferroptosis-based approaches that address tumor heterogeneity, immune interactions, and metabolic adaptations are crucial for overcoming therapy resistance. Refining ferroptosis-targeted strategies by incorporating metabolic, immune, and genetic considerations can lead to more durable and effective therapies, ultimately transforming glioblastoma treatment and improving patient outcomes.

DOI: https://doi.org/10.1038/s41420-025-02744-x