Targeting metabolic reprogramming in glioblastoma as a new strategy to overcome therapy resistance DOI Creative Commons
Simona D’Aprile, Simona Denaro,

Anna Gervasi

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 26, 2025

Glioblastoma (GBM) is one of the deadliest tumors due to its high aggressiveness and resistance standard therapies, resulting in a dismal prognosis. This lethal tumor carries out metabolic reprogramming order modulate specific pathways, providing metabolites that promote GBM cells proliferation limit efficacy treatments. Indeed, remodels glucose metabolism undergoes Warburg effect, fuelling glycolysis even when oxygen available. Moreover, recent evidence revealed rewiring nucleotide, lipid iron metabolism, not only an increased growth, but also radio- chemo-resistance. Thus, while on hand advantage for GBM, other it may represent exploitable target hamper progression. Lately, number studies focused drugs targeting uncover their effects therapy resistance, demonstrating some these are effective, combination with conventional treatments, sensitizing radiotherapy chemotherapy. However, heterogeneity could lead plethora alterations among subtypes, hence treatment might be effective proneural mesenchymal ones, which more aggressive resistant approaches. review explores key mechanisms involvement highlighting how acts as double-edged sword taking into account pathways seem offer promising options GBM.

Language: Английский

Comprehensive Analysis Identifies THEMIS2 as a Potential Prognostic and Immunological Biomarker in Glioblastoma DOI Creative Commons
Jianan Chen, Qiong Wu, Anders Berglund

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 66 - 66

Published: Jan. 7, 2025

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by its ability to evade the immune system, hindering efficacy of current immunotherapies. Recent research has highlighted important role immunosuppressive macrophages in microenvironment (TME) driving this evasion. In study, we are first identify THEMIS2 as key regulator tumor-associated macrophage (TAM)-mediated immunosuppression GBM. We found that high expression associated with poor patient outcomes and increased infiltration cells, particularly macrophages. Functional analyses revealed THEMIS2's critical involvement immune-related pathways, including response activation, mononuclear cell differentiation, positive regulation cytokine production. Additionally, single-cell RNA sequencing data demonstrated were phagocytosis, suppression, enhanced growth. These findings suggest could serve both prognostic marker therapeutic target for enhancing anti-tumor immunity

Language: Английский

Citations

0
Three-dimensional patient-derived models of glioblastoma retain intra-tumoral heterogeneity DOI Creative Commons
Zachery Moore, Claire Storey, Daniel V. Brown

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract The intra- and inter-tumoral heterogeneity of glioblastoma represents a significant therapeutic challenge, as well difficulty in generating reliable models for vitro studies. Historical 2D adherent cell lines do not recapitulate this complexity, whereas both patient-derived neurospheres (PDN) organoids (PDO) demonstrate intra-tumoral heterogeneity. Here, we quantify the tumor composition from matched established same primary using series multi-omic interrogations. We find that genomic, epigenomic tissue. Furthermore, single-nuclei RNA sequencing revealed subset containing small numbers non-malignant cells neuron immune lineages. Harnessing PDN models, reveal impact temozolomide chemotherapy on individual states, altering tumors over time response to treatment. Our data confirms patient providing platform state refined Key Points Generation neurosphere organoid resected GBM tissue Neurosphere exhibit greater proliferative signatures Both genomic features Single-nuclei reveals enable interrogation responses context Importance study Patient derived can be powerful tools when they faithfully which are derived. In glioblastoma, have been used studies, however differences between these recapitulation remain fully characterized. To address this, performed profiling PDO generated across range modalities, model systems high level resemblance tissue, critically, maintain composition. importance modeling was demonstrated where treatment specifically alters abundance MES-like AC-like cells. findings effectively preserve cellular heterogeneity, alterations, methylation transcriptomic features, highly suitable glioblastoma’s complex landscape.

Language: Английский

Citations

0
It’s all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma DOI Creative Commons

Rebeca Yakubov,

Ramneet Kaloti,

Phooja Persaud

et al.

Journal of Neuro-Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

The receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK signaling pathway is one of the most tumorigenic pathways in cancer, with its hyperactivation strongly linked to aggressive nature glioblastoma (GBM). Although extensive research has focused on developing therapeutics targeting this pathway, clinical success remains elusive due emergence resistance mechanisms. This review investigates how inhibition RTK/Ras/Raf/MEK/ERK alters transcription factors, contributing acquired mechanisms GBM. It also highlights critical role factor dysregulation therapeutic resistance. Findings from key studies GBM were synthesized explore targeted therapies, radiation, and chemotherapy. that factors undergo significant following inhibition, Transcription are promising targets for overcoming treatment GBM, cotreatment strategies combining inhibitors factor-targeted therapies presenting a novel approach. Despite challenges complex structures interactions, advancements drug development precision technologies hold great potential. Continued essential refine these improve outcomes other cancers.

Language: Английский

Citations

0
The Multifaceted Roles of MicroRNA-181 in Stem Cell Differentiation and Cancer Stem Cell Plasticity DOI Creative Commons
Chun Yang, Rui Wang, Pierre Hardy

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 132 - 132

Published: Jan. 17, 2025

Stem cells are undifferentiated or partially differentiated with an extraordinary ability to self-renew and differentiate into various cell types during growth development. The epithelial–mesenchymal transition (EMT), a critical developmental process, enhances stem cell-like properties in cells, is associated both normal function the formation of cancer cells. Cell stemness EMT often coexist interconnected contexts. Cancer tumor population that drives tumorigenesis, progression, drug resistance, metastasis. differentiation generation regulated by numerous molecules, including microRNAs (miRNAs). These miRNAs, particularly through modulation EMT-associated factors, play major roles controlling This review presents up-to-date summary regulatory miR-181 human stemness. We outline studies from current literature summarize miR-181-controlled signaling pathways responsible for driving emergence Given its role regulating stemness, promising target influencing fate. Modulation expression has been found be altered cells’ biological behaviors significantly improve treatment outcomes. Additionally, we discuss challenges miRNA-based therapies targeted delivery nanotechnology-based systems.

Language: Английский

Citations

0
Targeting metabolic reprogramming in glioblastoma as a new strategy to overcome therapy resistance DOI Creative Commons
Simona D’Aprile, Simona Denaro,

Anna Gervasi

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 26, 2025

Glioblastoma (GBM) is one of the deadliest tumors due to its high aggressiveness and resistance standard therapies, resulting in a dismal prognosis. This lethal tumor carries out metabolic reprogramming order modulate specific pathways, providing metabolites that promote GBM cells proliferation limit efficacy treatments. Indeed, remodels glucose metabolism undergoes Warburg effect, fuelling glycolysis even when oxygen available. Moreover, recent evidence revealed rewiring nucleotide, lipid iron metabolism, not only an increased growth, but also radio- chemo-resistance. Thus, while on hand advantage for GBM, other it may represent exploitable target hamper progression. Lately, number studies focused drugs targeting uncover their effects therapy resistance, demonstrating some these are effective, combination with conventional treatments, sensitizing radiotherapy chemotherapy. However, heterogeneity could lead plethora alterations among subtypes, hence treatment might be effective proneural mesenchymal ones, which more aggressive resistant approaches. review explores key mechanisms involvement highlighting how acts as double-edged sword taking into account pathways seem offer promising options GBM.

Language: Английский

Citations

0