Integrated proteomics and N-glycoproteomic characterization of glioblastoma multiform revealed N-glycosylation heterogeneities as well as alterations in sialyation and fucosylation DOI Creative Commons
Mingjun Hu,

Kaiyue Xu,

Ge Yang

et al.

Clinical Proteomics, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 8, 2025

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. Notwithstanding tremendous efforts having been put in multi-omics research to profile dysregulated molecular mechanisms and cellular pathways, there still a lack of understanding about glycoproteomic GBM. Glycosylation as one important post-translational modifications crucial regulating cell proliferation relevant oncogenic pathways. In study, we systematically profiled N-glycoproteomics para-cancerous cancerous tissues from GBM patients reveal site-specific N-glycosylation pattern defined by intact glycopeptides. We identified quantified 1863 distinct glycopeptides (IGPs) with 161 N-linked glycan compositions 326 glycosites. There were 396 IGPs 43 glycoproteins differed between adjacent Then, proteomic data combined, normalized glycosylation alteration was calculated determine whether difference attributed global protein levels or glycosylation. The altered triggered N-glycans glycoprotein abundance, well glycosite heterogeneity, demonstrated. Ultimately, an examination overall revealed positive contribution sialylated or/and fucosylated glycans. Overall, dataset highlighted complexity profiling at translational levels, providing valuable information for novel therapeutic approaches specific detection strategies.

Language: Английский

Shaping the brain vasculature in development and disease in the single-cell era DOI Open Access
Thomas Wälchli, Jeroen Bisschop, Peter Carmeliet

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(5), P. 271 - 298

Published: March 20, 2023

Language: Английский

Citations

77
Glioblastoma: An Update in Pathology, Molecular Mechanisms and Biomarkers DOI Open Access
Zhong Lan, Xin Li, Xiao-Qin Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 3040 - 3040

Published: March 6, 2024

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances understanding molecular pathogenesis biology this past decade, prognosis for GBM patients remains poor. characterized by aggressive biological behavior high degrees inter-tumor intra-tumor heterogeneity. Increased cellular heterogeneity may not only help more accurately define specific subgroups precise diagnosis but also lay groundwork successful implementation targeted therapy. Herein, we systematically review key achievements pathogenesis, mechanisms, biomarkers decade. We discuss pathology GBM, including genetics, epigenetics, transcriptomics, signaling pathways. that have potential clinical roles. Finally, new strategies, current challenges, future directions discovering therapeutic targets will be discussed.

Language: Английский

Citations

35
Protein kinase inhibitors as targeted therapy for glioblastoma: a meta-analysis of randomized controlled clinical trials DOI Creative Commons
José Pinto-Fraga, Celia García‐Chico, Simone Lista

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107528 - 107528

Published: Jan. 8, 2025

Glioblastoma (GBM) is the most common and lethal primary brain tumor. The standard treatment for newly diagnosed GBM includes surgical resection, when feasible, followed by radiotherapy temozolomide-based chemotherapy. Upon disease progression, anti-vascular endothelial growth factor-A (VEGF-A) monoclonal antibody bevacizumab, can be considered. Given limited efficacy of pharmacological treatments, particularly recurrent disease, several molecularly targeted interventions have been explored, such as small-molecule protein kinase inhibitors (PKIs), inhibiting tyrosine factor receptors downstream signaling pathways involved in angiogenesis infiltrative behavior. This meta-analysis, based on searches PubMed Web Of Science, evaluated 12 randomized controlled trials (RCTs) examining PKIs patients with or GBM. Pooled analysis shared clinical outcomes - progression-free survival (PFS) overall (OS) revealed a lack significant improvements use PKIs. In GBM, no differences were observed median [-1.02 months, 95% confidence interval (CI), -2.37-0.32, p=0.14] pooled [hazard ratio (HR)=1.13, CI, 0.95-1.35, p=0.17) OS, (0.34 -0.9-1.58, p=0.60) (HR=0.98, 0.76-1.27, p=0.89) PFS, comparing PKI addition to chemo-radiotherapy versus alone. three different analyses conducted: other combined treatments those alone, treatments. Also, across these analyses, benefits found. For instance, OS PFS showed difference (-0.78 -2.12-0.55, p=0.25; -0.23 -0.79-0.34, p=0.43, respectively), similar non-significant results (OS: HR=0.89, 0.59-1.32, p=0.55; PFS: HR=0.83, 0.63-1.11, p=0.21). Despite negative findings, some data indicate improved subset treated certain (i.e., regorafenib) encourage further research identify better blood-brain barrier penetration lower risk resistance development.

Language: Английский

Citations

2
Targeting Glioblastoma Stem Cells: A Review on Biomarkers, Signal Pathways and Targeted Therapy DOI Creative Commons

Xuejia Tang,

Chenghai Zuo,

Pengchao Fang

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: July 8, 2021

Glioblastoma (GBM) remains the most lethal and common primary brain tumor, even after treatment with multiple therapies, such as surgical resection, chemotherapy, radiation. Although great advances in medical development improvements therapeutic methods of GBM have led to a certain extension median survival time patients, prognosis poor. The cause its dismal outcomes is high rate tumor recurrence, which closely related resistance standard therapies. During last decade, glioblastoma stem cells (GSCs) been successfully isolated from GBM, it has demonstrated that these are likely play an indispensable role formation, maintenance, recurrence tumors, indicating GSCs crucial target for treatment. Herein, we summarize current knowledge regarding GSCs, their signaling pathways, mechanisms, crosstalk linking microenvironment or niche. Subsequently, present framework targeted therapy based on direct strategies, including blockade pathways necessary overcome prevent function, promotion GSC differentiation, virotherapy, indirect targeting perivascular, hypoxic, immune niches GSCs. In summary, provides tremendous opportunity revolutionary approaches improve despite variety challenges.

Language: Английский

Citations

78
From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress DOI Creative Commons
Brittany Dewdney, Misty R. Jenkins, Sarah A. Best

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 20, 2023

Glioblastoma, a rare, and highly lethal form of brain cancer, poses significant challenges in terms therapeutic resistance, poor survival rates for both adult paediatric patients alike. Despite advancements cancer research driven by technological revolution, translating our understanding glioblastoma pathogenesis into improved clinical outcomes remains critical unmet need. This review emphasises the intricate role receptor tyrosine kinase signalling pathways, epigenetic mechanisms, metabolic functions tumourigenesis resistance. We also discuss extensive efforts over past two decades that have explored targeted therapies against these pathways. Emerging approaches, such as antibody-toxin conjugates or CAR T cell therapies, offer potential specifically targeting proteins on surface. Combination strategies incorporating protein-targeted therapy immune-based demonstrate great promise future research. Moreover, gaining insights cell-of-origin treatment response holds to advance precision medicine approaches. Addressing is crucial improving moving towards more effective therapies.

Language: Английский

Citations

39
Emerging Perspectives on the Antiparasitic Mebendazole as a Repurposed Drug for the Treatment of Brain Cancers DOI Open Access
Daniela Meco, Giorgio Attinà, Stefano Mastrangelo

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1334 - 1334

Published: Jan. 10, 2023

Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase number of possible, effective anticancer drugs. The use ways other than their FDA-approved indications could offer novel avenues such as bypassing chemoresistance recurrence seen with conventional therapy treatment; moreover, it can safe economic for combination therapy. Recent works have demonstrated properties Mebendazole. This synthetic benzimidazole proved against broad spectrum intestinal Helminthiasis. Mebendazole penetrate blood-brain barrier has been shown inhibit malignant progression glioma by targeting signaling pathways related cell proliferation, apoptosis, or invasion/migration, increasing sensitivity cells chemotherapy radiotherapy. Moreover, several preclinical models ongoing clinical trials explore efficacy multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous carcinoma, breast gastrointestinal lung adrenocortical prostate head neck cancer. present review summarizes central literature regarding effects MBZ cancer lines, animal tumor models, suggest possible strategies economical combinations therapies might be an excellent candidate treatment tumors because its both when used monotherapy enhancement standard chemotherapeutics radiotherapy, due effectiveness on angiogenesis inhibition, cycle arrest, apoptosis induction, critical involved Hedgehog signaling. Therefore, attention repurposing recently increased potential versatility significant implications, reducing care costs optimizing existing therapies. Using treatments essential, particularly current therapeutics patients fail.

Language: Английский

Citations

31
Molecular crosstalk between GPCR and receptor tyrosine-protein kinase in neuroblastoma: molecular mechanism and therapeutic implications DOI

Kousik Maparu,

Dhrita Chatterjee,

Ramandeep Kaur

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(5)

Published: March 23, 2025

Language: Английский

Citations

1
Systematic comprehension of genomics and mutational landscape of Glioma: A goal towards advanced therapeutics DOI
Tikam Chand Dakal, Vipin Ranga, Ganesh S. Kakde

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery DOI Creative Commons

Harpinder Kaur Brar,

Jiney Jose, Zimei Wu

et al.

Pharmaceutics, Journal Year: 2022, Volume and Issue: 15(1), P. 59 - 59

Published: Dec. 24, 2022

Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy primarily limited by poor distribution due presence of blood–brain barrier (BBB). This review focuses on TKIs in therapy provides insight into reasons behind unsuccessful clinical trials despite success treating other cancer types. The main section dedicated use promising drug delivery strategies targeted tumors. Use can help enhance GBM. Among various approaches used bypass or cross BBB, utilizing nanocarriers a strategy augment pharmacokinetic properties overcome limitations. because advantages ability chemical stabilization circulation, passive active targeting tumor, modulation release from carrier, possibility be delivered via non-invasive intranasal route.

Language: Английский

Citations

31
Glioblastoma Stem Cells—Useful Tools in the Battle against Cancer DOI Open Access

Silvia Mara Baez Rodriguez,

Georgiana-Adeline Staicu, Ani-Simona Sevastre

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4602 - 4602

Published: April 21, 2022

Glioblastoma stem cells (GSCs) are with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked tumor cell heterogeneity. Most standard treatments fail completely eradicate GSCs, causing the recurrence of disease. GSCs could represent one reason for low efficacy cancer therapy short relapse time. Nonetheless, experimental data suggest presence therapy-resistant explain recurrence. Therefore, effectively target comprehensive understanding their biology survival developing mechanisms during treatment is mandatory. This review provides an overview molecular features, microenvironment, detection, targeting strategies essential information required efficient therapy. Despite outstanding results in oncology, researchers still novel strategies, which be present hypoxic regions invasive edge glioblastoma.

Language: Английский

Citations

30