Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings

Abstract

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management.

Keywords: central nervous system; glioblastoma; molecular biology; target therapy.

Figure 1

PRISMA flowchart.

Figure 2

Geographical distribution of research conduction.

Figure 3

Temporal distribution of research of molecular target therapy of GBMs.

Figure 4

Study design, type of targeted therapy, mechanism, and combination with temozolomide. Legend: PKP—Protein Kinase Pathway Group; CCRM—Cell Cycle-Related Mechanisms; MT—Microenvironmental Mechanisms; IT—Immunomodulatory Targets; OT—Other Targets.

Figure 5

Common molecular pathways associated with target therapy of GBM. Legend: EGF—Epidermal Growth Factor; VEGF—Vascular Endothelial Growth Factor; JAK—Janus Kinase; STAT—Signal Transducer and Activator of Transcription; Wnt—Wingless-Related Integration Site; Cyclin—Regulatory proteins involved in cell cycle progression; β Catenin—Beta-Catenin; RAS—Rat Sarcoma; GTP—Guanosine Triphosphate; BRAF—B-Raf Proto-Oncogene; MEK—Mitogen-Activated Protein Kinase Kinase; ERK—Extracellular Signal-Regulated Kinase; PI3K—Phosphatidylinositol 3-Kinase; Akt—Protein Kinase B; mTOR—Mammalian Target of Rapamycin; HIFa—Hypoxia-Inducible Factor alpha; CDK—Cyclin-Dependent Kinase; MDM2—Mouse Double Minute 2 Homolog.