Targeting Several Biologically Reported Targets of Glioblastoma Multiforme by Assaying 2D and 3D Cultured Cells

Area of Science:

• Neuro-oncology
• Molecular Biology
• Drug Discovery

Background:

• Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, accounting for 70% of central nervous system malignancies.
• Current treatments offer limited efficacy, with a median survival of approximately 15 months post-therapy.
• Identifying novel therapeutic targets and effective ligands is crucial for improving GBM patient outcomes.

Purpose of the Study:

• To synthesize and screen novel ligands targeting proteins implicated in anticancer effects.
• To evaluate the antiproliferative activity of these ligands on glioblastoma stem cells (GSCs) in 2D and 3D culture models.
• To identify the most promising therapeutic targets for GBM treatment.

Main Methods:

• Development of diverse ligands targeting histone deacetylases (HDACs), G protein-coupled estrogen receptor 1 (GPER), estrogen receptor-beta (ERβ), and NADPH oxidase (NOX).
• Screening of these ligands on 2D and 3D glioblastoma stem cell (GSC) cultures.
• Assessment of antiproliferative properties of the tested compounds.

Main Results:

• Several developed ligands demonstrated anticancer potential.
• Specific histone deacetylase (HDAC) inhibitors exhibited significant antiproliferative properties against GSCs in 3D cultures at concentrations of 21-32 µM.
• The study identified potential efficacy of targeting HDACs in GBM.

Conclusions:

• Histone deacetylase (HDAC) inhibitors show promise as a therapeutic strategy for glioblastoma.
• HDACs appear to be relevant targets for modulating antiproliferative effects in 3D GSC cultures.
• Further experimental studies are warranted to validate these findings and develop targeted therapies for glioblastoma.