Glioblastoma Therapy: Past, Present and Future

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2529 - 2529

Published: Feb. 21, 2024

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians researchers, no significant improvement in survival has achieved since Stupp protocol became standard care (SOC) 2005. Despite multimodality treatments, recurrence is almost universal with rates under 2 years after diagnosis. Here, we discuss recent progress our understanding GB pathophysiology, particular, importance glioma stem cells (GSCs), tumor microenvironment conditions, epigenetic mechanisms involved growth, aggressiveness recurrence. The discussion on therapeutic strategies first covers SOC treatment targeted therapies that shown to interfere different signaling pathways (pRB/CDK4/RB1/P16

Language: Английский

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Glut-3 Gene Knockdown as a Potential Strategy to Overcome Glioblastoma Radioresistance

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2079 - 2079

Published: Feb. 8, 2024

The hypoxic pattern of glioblastoma (GBM) is known to be a primary cause radioresistance. Our study explored the possibility using gene knockdown key factors involved in molecular response hypoxia, overcome GBM We used U87 cell line subjected chemical hypoxia generated by CoCl2 and exposed 2 Gy X-rays, as single or combined treatments, evaluated expression changes biomarkers Warburg effect, cycle control, survival identify best targets knocked-down, among those directly activated HIF-1α transcription factor. By this approach, glut-3 pdk-1 genes were chosen, effects their morpholino-induced silencing exploring proliferative rates modifications above-mentioned biomarkers. found that, after induced greater decrease proliferation, compared strong upregulation glut-1 ldha, sign restore anaerobic glycolysis pathway. Overall, offered better chance controlling use pyruvate proliferation rate reduction, suggesting it suitable target

Language: Английский

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Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 18, 2024

Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic elusive. A major hurdle in treatment success is ability of cells, particularly stem cells (CSCs), resist therapy. These CSCs possess unique abilities, including self-renewal, differentiation, repair, which drive tumor progression chemotherapy resistance. The resilience linked certain signaling pathways. Tumors with pathway-dependent often develop genetic resistance, whereas those pathway-independent undergo epigenetic changes that affect gene regulation. can evade cytotoxic drugs, radiation, apoptosis by increasing drug efflux transporter activity activating survival mechanisms. Future research should prioritize identification new biomarkers molecules better understand use cutting-edge approaches, such as bioinformatics, genomics, proteomics, nanotechnology, offers potential solutions this challenge. Key include developing targeted therapies, employing nanocarriers precise delivery, focusing on CSC-targeted pathways Wnt, Notch, Hedgehog Additionally, investigating multitarget inhibitors, immunotherapy, nanodrug delivery systems critical overcoming resistance cells.

Language: Английский

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Navigating the Immune Maze: Pioneering Strategies for Unshackling Cancer Immunotherapy Resistance

Cancers, Journal Year: 2023, Volume and Issue: 15(24), P. 5857 - 5857

Published: Dec. 15, 2023

Cancer immunotherapy has ushered in a transformative era oncology, offering unprecedented promise and opportunities. Despite its remarkable breakthroughs, the field continues to grapple with persistent challenge of treatment resistance. This resistance not only undermines widespread efficacy these pioneering treatments, but also underscores pressing need for further research. Our exploration into intricate realm cancer reveals various mechanisms at play, from primary secondary significant impact genetic epigenetic factors, as well crucial role tumor microenvironment (TME). Furthermore, we stress importance devising innovative strategies counteract this resistance, such employing combination therapies, tailoring immune checkpoints, implementing real-time monitoring. By championing state-of-the-art methods, anticipate paradigm that blends personalized healthcare improved options is firmly committed patient welfare. Through comprehensive multifaceted approach, strive tackle challenges aspiring elevate beacon hope patients around world.

Language: Английский

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Presence of Fragmented Intratumoral Thrombosed Microvasculature in the Necrotic and Peri‐Necrotic Regions on SWI Differentiates IDH Wild‐Type Glioblastoma From IDH Mutant Grade 4 Astrocytoma

Journal of Magnetic Resonance Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Background Isocitrate dehydrogenase (IDH) wild‐type (IDH wt ) glioblastomas (GB) are more aggressive and have a poorer prognosis than IDH mutant mt tumors, emphasizing the need for accurate preoperative differentiation. However, distinct imaging biomarker differentiation mostly lacking. Intratumoral thrombosis has been reported as histopathological GB. Purpose To evaluate fragmented intratumoral thrombosed microvasculature (FTV) signs on susceptibility‐weighted (SWI) distinguishing tumors. Study Type Retrospective. Subjects Ninety‐seven treatment‐naïve patients with histopathologically confirmed GB (54 males, 26 females) grade 4 astrocytoma (13 females). Field Strength/Sequence 3‐T, SWI, fluid‐attenuated‐inversion‐recovery (FLAIR), T 1 ‐weighted, 2 PD‐weighted, post‐contrast ‐weighted dynamic‐contrast‐enhanced (DCE)‐MRI. Assessment SWI data were evaluated by three experienced neuroradiologists (S.S., 11 years; J.S., 15 R.K.G., 40 years of experience), who assessed FTV presence in necrotic peri‐necrotic regions. was identified susceptibility signal having minimal or no interslice connections. Quantitative DCE‐MRI parameters derived using first‐pass‐analysis extended Tofts model. FLAIR abnormal, contrast‐enhancing, regions segmented in‐house developed U‐Net architecture. Statistical Tests Fleiss' Kappa, Cohen's Shapiro–Wilk test, t tests Mann–Whitney U receiver‐operating characteristic (ROC) analysis, confusion matrix. A P ‐value <0.05 considered statistically significant. Results kappa test provided 91% inter‐rater agreement, intrarater agreement ranged from 81% to 97%. The raters' accuracy 92% 94%. Some quantitative (CBV, Ve, K trans significant differences differentiating . demonstrated 80.3% sensitivity 81.2% specificity, ROC analysis showing an AUC 0.77. Data Conclusion high Qualitative assessment showed almost perfect agreement. metrics also Plain Language Summary This study demonstrates that imaging, particularly visualization vasculature sign (SWI), effectively differentiates isocitrate glioblastoma astrocytomas. Over 90% displayed sign, specific absent cases. Perfusion such cerebral blood volume, elevated gliomas, reflecting vascular profiles. offers noninvasive diagnostic method, overcoming limitations histopathology. Despite like unequal sample sizes retrospective this underscores clinical potential improving glioma characterization aiding treatment planning. Level Evidence Technical Efficacy Stage

Language: Английский

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The Complexity of Malignant Glioma Treatment

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 879 - 879

Published: March 4, 2025

Malignant glioma is a highly aggressive, therapeutically non-responsive, and deadly disease with unique tumor microenvironment (TME). Of the 14 currently recognized described cancer hallmarks, five are especially implicated in malignant targetable repurposed drugs: stem-like cells, general, cells particular (GSCs), vascularization hypoxia, metabolic reprogramming, tumor-promoting inflammation sustained proliferative signaling. Each hallmark drives development, both individually through interactions other which TME plays critical role. To combat aggressive spatio-temporal heterogeneity driven by interactions, to overcome its therapeutic challenges, combined treatment strategy including anticancer therapies, drugs multimodal immunotherapy should be aim for future approaches.

Language: Английский

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The m6A RNA demethylase FTO promotes radioresistance and stemness maintenance of glioma stem cells

Cellular Signalling, Journal Year: 2025, Volume and Issue: 132, P. 111782 - 111782

Published: April 4, 2025

Language: Английский

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Hyperbaric oxygen promotes both the proliferation and chemosensitization of glioblastoma cells by inhibiting HIF1α/HIF2α-ABCG2

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: April 30, 2025

Introduction Hyperbaric oxygen enhances glioma chemosensitivity, but the mechanism remains unclear. Hypoxia is common in gliomas, and as main effector molecules of hypoxia, HIF1α HIF2α promote malignant progression by inhibiting cell apoptosis maintaining stemness. ABCG2 a marker protein tumor stem cells drug efflux transporter protein. This study aims to reveal detailed hyperbaric both proliferation chemosensitization. Methods Under hypoxic conditions, we investigated differences cycle, proliferation, apoptosis, LDH release, expression proteins mRNA. We also conducted studies on transcriptional regulation performed vivo experiments. Results It revealed that under HIF1α, HIF2α, are highly expressed, expression. After treatment, decreased, chemosensitivity increased. knocking out increased, decreased. ChIP-qPCR target promoter. Gain-and loss-of-function experiments suggested can proteins, inhibit progression. Conclusion confirmed through thereby promoting chemosensitization gliomas.

Language: Английский

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Current Understanding Regarding the Glioma Microenvironment and Impact of the Immune System

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 13 - 13

Published: March 7, 2025

High-grade gliomas are aggressive, primary, central nervous system tumors with low survival rates due to recurrence and resistance current therapy models. Recent studies have highlighted the importance between interaction of glioma cancer cells tumor microenvironment (TME). Cancer stem immune play a critical role in TME gliomas. TMEs include perivascular TME, hypoxic invasive each which evolved as our understanding involved cellular players has improved. This review discusses multidimensional aspects targeted therapies interactions specific focus on immunotherapies. Understanding complexities elucidating various tumor-cell will be for facilitating development novel precision strategies, ultimately enabling better patient outcomes.

Language: Английский

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Current Knowledge about the Peritumoral Microenvironment in Glioblastoma

Cancers, Journal Year: 2023, Volume and Issue: 15(22), P. 5460 - 5460

Published: Nov. 17, 2023

Glioblastoma is a deadly disease, with mean overall survival of less than 2 years from diagnosis. Recurrence after gross total surgical resection and adjuvant chemo-radiotherapy almost invariably occurs within the so-called peritumoral brain zone (PBZ). The aim this narrative review to summarize most relevant findings about biological characteristics PBZ currently available in medical literature. presents several peculiar characteristics. cellular landscape area different that healthy tissue characterized by mixture cell types, including tumor cells (seen 30% cases), angiogenesis-related endothelial cells, reactive astrocytes, glioma-associated microglia/macrophages (GAMs) anti-inflammatory polarization, tumor-infiltrating lymphocytes (TILs) an “exhausted” phenotype, stromal (GASCs). From genomic transcriptomic point view, compared core tissue, “half-way” pattern upregulation genes related angiogenesis, extracellular matrix, senescence stemness features downregulation suppressor genes. This illustrates transition pre-malignant microenvironment constitutes base for GBM progression/recurrence. Understanding could be developing more effective treatments prevent development recurrence.

Language: Английский

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