Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy DOI Creative Commons

Karen Olthoff,

Ayelén D. Nigra, Laura N. Milla Sanabria

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(12), P. 1192 - 1192

Published: Nov. 26, 2024

Background: Glioblastoma (GBM) is the most common and deadly type of brain cancer in adults. Dysregulation receptor tyrosine kinase pathways, such as epidermal growth factor (EGFR), contributes to therapeutic resistance. Drugs that inhibit activity monoclonal antibodies against EGFR are strategies used clinical trials. Photodynamic therapy (PDT) a tumor treatment involves administration photosensitizing drug, followed by its activation with visible light, which causes cell death due oxidative stress. Although PDT helps prolong median survival patients GBM, complete remission has not been achieved. Populations GBM cells have obtained from T98G line resistant methyl-5-aminolevulinic acid (Me-ALA) for characterization, comparing them original parental population. Objective: The objective this work was evaluate general response when inhibited drug erlotinib. Methods Results: It observed inhibitor combination reduced viability (MTT) populations compared alone. Furthermore, PpIX content (flow cytometry) increased population were incubated Me-ALA Erlotinib prevented proliferation spheroids. Wound closure both PDT-resistant populations. Conclusions: Our results indicate would be relevant resistance PDT.

Language: Английский

Serendipity in Neuro-Oncology: The Evolution of Chemotherapeutic Agents DOI Open Access

Denise Nadora,

Shawyon Ezzati, Brandon Bol

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2955 - 2955

Published: March 25, 2025

The development of novel therapeutics in neuro-oncology faces significant challenges, often marked by high costs and low success rates. Despite advances molecular biology genomics, targeted therapies have had limited impact on improving patient outcomes brain tumors, particularly gliomas, due to the complex, multigenic nature these malignancies. While efforts been made design drugs that target specific signaling pathways genetic mutations, clinical rational approaches remains sparse. This review critically examines landscape drug discovery, highlighting instances where serendipity has led breakthroughs, such as unexpected efficacy repurposed off-target effects proved beneficial. By exploring historical contemporary cases, we underscore role chance discovery impactful therapies, arguing embracing alongside may enhance future development.

Language: Английский

Citations

0
The Co-Expression and Cellular Location of HER Family Members, EGFRvIII, Putative Cancer Stem Cell Biomarkers CD44 and CD109 in Patients with Glioblastoma, and Their Impacts on Prognosis DOI Open Access

Ermira Mulliqi,

Said Khelwatty,

Izhar Bagwan

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1221 - 1221

Published: April 4, 2025

The aberrant expression and activation of HER family members is a known major oncogenic pathway for the proliferation, progression, metastasis wide range human malignancies. In this study, our aim was to examine relative prognostic significance all family, type III EGFR mutant (EGFRvIII), putative stem cell markers CD44 CD109 in patients with glioblastoma. levels wild-type (wtEGFR), HER2, HER3, HER4, EGFRvIII, CD44, were determined tumour specimens from 80 by immunohistochemistry. staining scored based on percentage positive cells, intensity, cellular location immunostaining. association between level biomarkers patient overall survival evaluated using Chi-squared, Kaplan-Meier curves, log-rank tests. At cut-off value ≥5% staining, 46% 75% (HER2), 19% (HER3), 71% (HER4), 85% 95% (CD44), 16% (CD109) cases these biomarkers. Interestingly, at same value, wtEGFR accompanied co-expression HER2 (35%), HER3 (0%), HER4 (30%), EGFRvIII (36%), (44%), HER2/EGFRvIII (28%), HER2/CD44 (31%), EGFRvIII/CD44 (36%). addition, (65%), (15%), (63%), (83%), (16%), wtEGFR/HER2 55% had EGFRvIII/HER2/HER4/CD44. With exception expression, values cells which associated better [HR = 0.57 (p 0.038), HR 0.56 0.034)], there no significant other both univariate multivariate analysis. Conclusions Our results suggest that different CD109, occurs As therapy inhibitors have not been encouraging brain tumour, further investigation should determine whether such can be predictive response various types their potential as therapeutic targets co-targeted therapy.

Language: Английский

Citations

0
Application of EGFR-TKIs in brain tumors, a breakthrough in future? DOI Creative Commons

Shiying Feng,

Huiqin Liu, Chohee Yun

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 16, 2025

Brain tumors, both primary and secondary, represent a significant clinical challenge due to their high mortality limited treatment options. Primary brain such as gliomas meningiomas, metastases from cancers non-small cell lung cancer breast require innovative therapeutic strategies. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR -TKIs) have emerged promising option, particularly for tumors harboring EGFR mutations. This review examines the use of EGFR-TKIs in highlighting laboratory research findings. In metastases, shown potential controlling tumor improving patient outcomes. Advanced applications, nano-formulated combination therapies with other pathway inhibitors, are being investigated improve efficacy overcome resistance. Challenges treatment-related events, resistance mechanisms blood-brain barrier penetration remain hurdles. Addressing heterogeneity through personalized medicine approaches is critical optimizing EGFR-TKI therapies. highlights need continued refine these survival patients tumors.

Language: Английский

Citations

0
A Synopsis of Biomarkers in Glioblastoma: Past and Present DOI Creative Commons
Ligia Gabriela Tătăranu, Şerban Turliuc,

Radu Eugen Rizea

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(7), P. 6903 - 6939

Published: July 3, 2024

Accounting for 48% of malignant brain tumors in adults, glioblastoma has been great interest the last decades, especially biomolecular and neurosurgical fields, due to its incurable nature notable neurological morbidity. The major advancements technologies have positively influenced extent safe tumoral resection, while latest progress field GBM uncovered new potential therapeutical targets. Although currently no curative therapy, recent made management this disease, both from surgical molecular perspectives. main current therapeutic approach is multimodal consists intervention, radiotherapy, chemotherapy, mostly with temozolomide. most patients will develop treatment resistance tumor recurrence after removal, regarding contributed a better understanding pathology management. Over past few specific biomarkers discovered that helped predict prognosis responses improvements survival rates.

Language: Английский

Citations

3
Preparation, Characterization, DFT Calculations, biological evaluations and Molecular docking studies of benzimidazolium-based N-heterocyclic carbenes and selenium-adducts DOI

Areeba Altaf,

Faisal Jamil,

Munazzah Yaqoob

et al.

Inorganica Chimica Acta, Journal Year: 2024, Volume and Issue: 574, P. 122348 - 122348

Published: Aug. 30, 2024

Language: Английский

Citations

2
The Invasion Factor ODZ1 Is Upregulated through an Epidermal Growth Factor-Induced Pathway in Primary Glioblastoma Cells DOI Open Access
Carlos Velásquez, Olga Gutiérrez, María Carcelén

et al.

Published: March 14, 2024

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion surrounding parenchyma through activation a RhoA-ROCK pathway. also described GBM can control expression transcriptional mechanisms triggered by binding IL-6 to its receptor hypoxic environment. Epidermal growth factor (EGF) plays key role in invasive capacity GBM. However, molecular enable tumor acquire morphological changes migrate out from core not been fully characterized. Here we show EGF is able induce primary cells. analysed levels (EGFR) 20 cell lines found 19 them flow cytometry. selected two do or express EGFR EGFR-expressing responded ligand increasing at mRNA level. Moreover, blockade EGF-EGFR Cetuximab, inhibition p38 MAPK pathway siRNA-mediated knockdown MAPK11 (p38 MAPK) reduced induction response EGF. Overall, may activate an EGFR-mediated signalling p38 MAPK, upregulate ODZ1, which initiate for invade parenchyma. These data identify new candidate novel therapeutic approaches.

Language: Английский

Citations

1
Discovery of a Therapeutic Agent for Glioblastoma Using a Systems Biology-Based Drug Repositioning Approach DOI Open Access
Ali Kaynar, Mehmet Özcan, Xiangyu Li

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7868 - 7868

Published: July 18, 2024

Glioblastoma (GBM), a highly malignant tumour of the central nervous system, presents with dire prognosis and low survival rates. The heterogeneous recurrent nature GBM renders current treatments relatively ineffective. In our study, we utilized an integrative systems biology approach to uncover molecular mechanisms driving progression identify viable therapeutic drug targets for developing more effective treatment strategies. Our analysis revealed elevated expression CHST2 in tumours, designating it as unfavourable prognostic gene GBM, supported by data from two independent cohorts. Further, pinpointed WZ-4002 potential candidate modulate through computational repositioning. directly targeted EGFR (ERBB1) ERBB2, affecting their dimerization influencing activity adjacent genes, including CHST2. We validated findings treating U-138 MG cells WZ-4002, observing decrease protein levels reduction cell viability. summary, research suggests that may effectively offering promising avenue efficient strategies patients.

Language: Английский

Citations

1
Prospective Molecular Targets for Natural Killer Cell Immunotherapy against Glioblastoma Multiforme DOI Creative Commons

Luke C. Cooksey,

Derek C. Friesen,

Enrique D. Mangan

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(18), P. 1567 - 1567

Published: Sept. 17, 2024

Glioblastoma multiforme (GBM) is the most common type of primary malignant brain tumor and has a dismal overall survival rate. To date, no GBM therapy yielded successful results in for patients beyond baseline surgical resection, radiation, chemotherapy. Immunotherapy taken oncology world by storm recent years there been movement from researchers to implement immunotherapy revolution into treatment. Natural killer (NK) cell-based immunotherapies are rising candidate treat multiple therapeutic vantage points: monoclonal antibody targeting tumor-associated antigens (TAAs), immune checkpoint inhibitors, CAR-NK cell therapy, Bi-specific engagers (BiKEs), more. NK therapies often focus on targeting. Here, we reviewed some targets analyzed fight relevant cells: EGFR, HER2, CD155, IL-13Rα2. We further propose investigating Lectin-like Transcript 1 (LLT1) surface proliferating nuclear antigen (csPCNA) as immunotherapy.

Language: Английский

Citations

1
Structure activity relationship for anticancer activities of spirooxindole derivatives: A comprehensive review DOI

Gandhar Pradhan,

Kapil Juvale

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 154, P. 107975 - 107975

Published: Nov. 19, 2024

Language: Английский

Citations

1
The Invasion Factor ODZ1 Is Upregulated through an Epidermal Growth Factor Receptor-Induced Pathway in Primary Glioblastoma Cells DOI Creative Commons
Carlos Velásquez, Olga Gutiérrez, María Carcelén

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(9), P. 766 - 766

Published: April 30, 2024

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodeling of glioblastoma (GBM) cells and invasion surrounding parenchyma through activation a RhoA–ROCK pathway. also described GBM can control expression transcriptional mechanisms triggered by binding IL-6 to its receptor hypoxic environment. Epidermal growth factor (EGF) plays key role in invasive capacity GBM. However, molecular enable tumor acquire morphological changes migrate out from core not been fully characterized. Here, we show EGF is able induce primary cells. analyzed levels (EGFR) 20 cell lines found 19 them flow cytometry. selected two do or express EGFR EGFR-expressing responded ligand increasing at mRNA levels. Moreover, blockade EGF-EGFR Cetuximab, inhibition p38 MAPK pathway, Additionally, siRNA-mediated knockdown MAPK11 (p38β MAPK) reduced induction response EGF. Overall, may activate an EGFR-mediated signaling pathway p38β MAPK, upregulate ODZ1, which initiate for invade parenchyma. These data identify new candidate EGF–EGFR novel therapeutic approaches.

Language: Английский

Citations

0