Exploring the potential of multiple receptors overexpressed on glioblastoma cells as biomarkers for the targeted therapy; a review

Glioblastoma multiforme (GBM), due to its complex and highly heterogeneous nature, remains one of the deadliest cancers in the world. However, advances in targeted therapy offer hope for improved GBM treatment through extensive research into receptor-mediated targeting approaches that exploit receptors overexpressed on the surface of GBM cells, including interleukin-13 receptor alpha 2 (IL-13Rα2), transferrin receptor (TfR), receptor tyrosine kinases (RTKs), and integrins. Nanoparticles such as liposomes, lactoferrin-based specialized nanocarriers, and gold nanoparticles functionalized with targeting ligands including Pep-1L, lactoferrin, and RGD peptides, and loaded with anticancer drugs such as temozolomide, gefitinib, and epirubicin, are being explored for targeted GBM therapy. These approaches have demonstrated promising preclinical outcomes, with several formulations in early-phase clinical trials to evaluate safety, pharmacokinetics, and therapeutic efficacy. Certain receptors, including periostin (POSTN) and chondroitin sulfate proteoglycan-4 (CSPG4), involved in tumor invasion, glioma stemness, and therapeutic resistance, remain relatively underexplored, presenting opportunities for further research. Despite these advances, clinical translation remains limited by nanoparticle-associated cytotoxicity and off-target effects. This highlights the need for future research focused on developing biodegradable and biocompatible nanomaterials, along with optimized ligand-guided designs, to improve safety and enhance translational feasibility in glioblastoma therapy. Literature search Methodology: [PubMed and Google Scholar; 2006-2026].